Mol. Hum. Reprod. Advance Access originally published online on April 27, 2006
Molecular Human Reproduction 2006 12(6):383-388; doi:10.1093/molehr/gal042
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Transcriptional expression of survivin and its splice variants in endometriosis
Department of Obstetrics and Gynecology, Osaka Medical College, Daigakumachi, Takatsuki, Osaka, Japan
1 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Osaka Medical College, 2–7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan. E-mail: gyn017{at}poh.osaka-med.ac.jp
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Abstract |
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Survivin is a novel inhibitor of apoptosis (IAP), and the two splice variants of survivin (survivin-2B and survivin-EX3) have been identified. Gene expression levels of survivin, survivin-2B and survivin-EX3 in 56 ectopic (16 peritoneal red and 16 peritoneal black lesions and 24 ovarian endometriomata) and 13 eutopic endometrial tissues surgically obtained from 42 women with endometriosis (group A) were compared with those in 16 control eutopic endometrium from 16 women without endometriosis (group B) by quantitative RT–PCR analysis. Survivin mRNA expression levels in ectopic endometriotic tissues were significantly higher than those in eutopic endometrium of groups A and B over the whole cycle. Red peritoneal lesions had higher gene expression levels of survivin than black lesions. In contrast, all tissue samples examined showed relatively lower gene expression levels of survivin-2B and survivin-EX3. No cyclic variation was found in survivin and the two splice variants, both in ectopic and in eutopic endometrium. Although there was no significant difference in the ratio of survivin-2B/survivin between ectopic and eutopic endometrium, the ratio of survivin-EX3/survivin in peritoneal endometriotic lesions was significantly higher than that of eutopic endometrium of groups A and B. These results suggest that survivin and survivin-EX3 may be closely linked to escape from apoptosis and the development of endometriosis.
Key words: apoptosis/endometriosis/splice variants/survivin
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Endometriosis is a common disease affecting 5–15% of women in the general population and 40% of women seeking infertility evaluation (Eskenazi and Warner, 1997
). Its aetiology is unclear, but it is thought to be because of the implantation and maintenance of disseminated uterine endometrium, predominantly on the ovary and pelvic peritoneum (Sampson, 1927; Jenkins et al., 1986). Normal epithelial cells undergo apoptosis when they separate from their primary tissue. However, spontaneous apoptosis of ectopic endometrial tissue is impaired in women with endometriosis, and its decreased susceptibility to apoptosis might participate in the growth and survival of endometriotic tissue (Gebel et al., 1998; Belliard et al., 2004).
Among the regulators of cell death, inhibitor of apoptosis (IAP) proteins have recently emerged as modulators of an evolutionarily conserved step in apoptosis, which may potentially involve the direct inhibition of terminal effector caspases 3 and 7 (Devereaux et al., 1997). Recently, a novel and structurally unique member of the IAP gene family-designated survivin was identified (Ambrosini et al., 1997). Unlike other IAP proteins, survivin was found during embryonic and fetal development, was completely down-regulated and undetectable in normal adult tissues and became prominently re-expressed in all of the most common human cancers (Ambrosini et al., 1997). In contrast, recent reports have demonstrated that survivin is also expressed in normal tissues, such as skin, endothelial cells and endometrium (Chiodino et al., 1999; Konno et al., 2000; O’Connor et al., 2000; O’Driscoll et al., 2003). Konno et al. (2000) indicated that survivin could play an important role in physiological homeostasis during the normal menstrual cycle. Moreover, we previously reported using semi-quantitative RT–PCR analysis that survivin gene was detected in ectopic and eutopic endometrium and that survivin gene expression was closely associated with reduction of apoptotic cells and invasive phenotype in endometriosis (Ueda et al., 2002). Survivin may be closely linked to escape from apoptosis of endometriotic tissue and the development of endometriosis.
The gene encoding for survivin has been located on chromosome 17q25. Two novel splice variants of survivin oriented at the same locus were recently described: survivin-2B and survivin-EX3 (Mahotka et al., 1999). Survivin-2B retains 69 bp of intron 2 as a novel exon (exon 2B) between exon 2 and exon 3. Survivin-EX3 is missing 118 bp of exon 3. On the basis of their transfection experiments, Mahotka et al. (1999) reported that the role of survivin-EX3 might be the conservation of anti-apoptotic properties, whereas the role of survivin-2B might be the reduction of the anti-apoptotic potential compared with that in survivin. Although Mahotka et al. (2002) and Yamada et al. (2003) succeeded in quantifying gene expression levels of survivin splice variants using benign or malignant kidney and brain tissue specimens, there has been no report on the expression pattern of these variants in human endometrium.
In the present study, we analysed gene expression levels of survivin and its splice variants in ectopic and eutopic endometrium using quantitative RT–PCR and evaluated the biological significance of survivin isoforms in the pathogenesis of endometriosis.
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Materials and methods |
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Patients and tissue samples
The subjects in this study were women of reproductive age undergoing laparoscopy or laparotomy for suspected endometriosis or benign tumours between December 1999 and February 2002. At the time of surgery, pelvic organs were examined carefully for the presence and extent of endometriosis. Stages of the disease and macroscopic findings of endometriotic lesions were classified according to the revised American Society for Reproductive Medicine (1997)
classification system. Patients who received sex-steroid derivatives or GnRH analogues within 1 year before the operation were excluded from the current study. This study was approved by our institutional review board, and all subjects signed informed consent forms. Forty-two women with endometriosis (group A) and 16 women without endometriosis (group B) were evaluated. Of the 42 women in group A, two had stage I, three had stage II, 10 had stage III and 27 had stage IV disease. Fifty-six ectopic endometriotic tissue specimens for mRNA analysis were removed with biopsy forceps under laparoscopy or laparotomy from the women in group A. Ectopic endometriotic tissues included 16 peritoneal red and 16 peritoneal black lesions and 24 ovarian endometriomata. Eutopic endometrial tissues were also collected by endometrial curettage from 13 women in group A. Sixteen control eutopic endometrial tissue specimens were obtained as described above from the group B without any findings of endometriosis on laparoscopy. The menstrual cycle phase for each subject was assigned based on the histologic evaluation of eutopic endometrium or basal body temperature. All tissue specimens were immediately frozen in liquid nitrogen and then stored at –80°C until use.
RNA isolation and cDNA preparation
RNA was extracted from homogenized tissue samples by a combination of initial phenol/chloroform extraction according to the RNA STAT-60 protocol (Tel-Test, Friendswood, TX, USA) and then SV-total RNA isolation kit extraction (Promega, Madison, WI, USA) according to the supplier’s recommendation. Contaminating residual genomic DNA was removed by digestion with RNase-free DNase (Promega). cDNA was prepared using at least 2 µg of total RNA and SUPERSCRIPT II reverse-transcriptase (GIBCO BRL Life Technologies, Gaithersburg, MD, USA) with random hexamers as primers and was finally dissolved in diethyl pyrocarbonate-treated water and then frozen at –20°C until use.
Quantitative RT–PCR analysis
Quantitative PCR amplification was performed with a LightCycler (Roche Diagnostics, Tokyo, Japan) according to the method reported by Yamada et al. (2003), with some modifications for each target gene. As an internal control, the expression of ß-actin mRNA was measured.
The primer pairs and hybridization probes for survivin and the two splice variants were as follows. The sequence of the common forward primer for survivin, survivin-2B and survivin-EX3 was 5'-CCACCGCATCTCTACATTCA-3' (NCBI BC008718
[GenBank]
90–109, NCBI AB028869
[GenBank]
74–93 and NCBI BC000784
[GenBank]
102–121, respectively). To distinguish between survivin and either of its splice variants, we designed the sequences of reverse primers to correspond to exon/exon borders of the complementary strand. The sequence of the reverse primer for survivin mRNA was 5'-TATGTTCCTCTATGGGGTCG-3' (NCBI BC008718
[GenBank]
255–274), for survivin-2B mRNA 5'-AGTGCTGGTATTACAG GCGT-3' (NCBI AB028869
[GenBank]
268–287) and for survivin-EX3 mRNA 5'-TTTC CTTTGCATGGGGTC-3' (NCBI BC000784
[GenBank]
268–285). The sequence of the common hybridization probe F for survivin, survivin-2B and survivin-EX3 was 5'-CAAGTCTGGCTCGTTCTCAGTGGG-3'-fluorescein isothiocyanate (FITC) (NCBI BC008718
[GenBank]
159–179, NCBI AB028869
[GenBank]
143–163 and NCBI BC000784
[GenBank]
171–191, respectively). The sequence of the common hybridization probe R for survivin, survivin-2B and surviving-EX3 was LC-5'-CAGTGGATGAAGCCAGCCTCG-3'-P (NCBI BC008718
[GenBank]
181–204, NCBI AB028869
[GenBank]
165–188 and NCBI BC000784
[GenBank]
193–216, respectively). The nucleotide sequences of primer pairs and probes for ß-actin mRNA were designed as previously described (Kanda et al., 2005).
Two microlitres of cDNA aliquots was subjected to amplification in a 20-µl reaction mixture containing 2 µl of LightCycler-FastStart Mix (Taq DNA polymerase, reaction buffer and deoxynucleoside triphosphate mix; Roche Molecular Biochemicals, Mannheim, Germany), 1 µl of sense and antisense primers (10 pM), 1 µl of hybridization probe R (8 pM), 1 µl of hybridization probe F (4 pM) and 3 mM of MgCl2 and sterile distilled water. After an initial denaturation at 95°C for 15 min, 40 cycles of denaturation at 95°C for 10 s, annealing at 62°C for 10 s and extension at 72°C for 10 s for the respective target genes were carried out on a Roche LightCycler System. A standard curve was generated using fluorescent data from the serial dilutions of the plasmid including a single PCR product for each gene. Data for survivin, survivin-2B and survivin-EX3 were normalized with the data for ß-actin. Each analysis was performed in triplicate.
Statistical analysis
All statistical calculations were carried out using Stat View statistical software. The significance of differences between groups was calculated by analysis of variance (ANOVA) with post hoc test. A P value <0.05 was accepted as statistically significant.
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Results |
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Survivin gene expression levels in each lesion
As summarized in Table I, gene expression levels of survivin in ectopic endometriotic tissues were significantly higher than those in eutopic endometrium of groups A and B over the whole cycle (P < 0.01) and either in the proliferative or in the secretory phase (P < 0.05). However, there was no significant difference in the expression levels of survivin between eutopic endometrium of groups A and B. Survivin mRNA expression levels in eutopic endometrium of groups A and B tended to be higher in the secretory phase than in the proliferative phase, but there was no statistically significant difference.
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Survivin-2B gene expression levels in each lesion
As summarized in Table II, quantitative RT–PCR analysis on survivin splice variants revealed that ectopic and eutopic endometrial tissues had extremely lower gene expression levels of survivin-2B over the whole cycle. There was no statistically significant difference in the expression levels of survivin-2B between ectopic and eutopic endometrium obtained from women of groups A and B, and no cyclic variation was found.
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Survivin-EX3 gene expression levels in each lesion
As summarized in Table III, ectopic and eutopic endometrial tissues had also relatively lower gene expression levels of survivin-EX3 over the whole cycle. Survivin-EX3 mRNA expression levels in ectopic endometriotic tissues tended to be higher than those in eutopic endometrium of groups A and B, but there was no statistically significant difference, and no cyclic variation was found.
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Gene expression levels of survivin and its splice variants in each peritoneal lesion
As summarized in Table IV, gene expression levels of survivin in peritoneal red and black lesions were significantly higher than those of survivin-2B and survivin-EX3 over the whole cycle (P < 0.01). Survivin mRNA expression levels in peritoneal red lesions were statistically higher than those in peritoneal black lesions in the proliferative phase (P < 0.05). There was no significant difference in the expression levels of the two splice variants between peritoneal red and black lesions either in the proliferative or in the secretory phase, and no cyclic variation was found.
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Expression patterns of survivin splice variants in ectopic and eutopic endometrium
We then compared the ratio of survivin splice variants/survivin between ectopic and eutopic endometrium. There was no statistically significant difference in the ratio of survivin-2B/survivin between ectopic endometriotic tissues and eutopic endometrium of groups A and B (Figure 1). In contrast, the ratio of survivin-EX3/survivin in peritoneal endometriotic lesions was significantly higher than that of eutopic endometrium of groups A and B, respectively (P < 0.01; Figure 2).
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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In this study, we analysed gene expression levels of survivin and its splice variants in ectopic and eutopic endometrial tissue samples using quantitative RT–PCR. In previous reports on the expression of survivin in endometriotic lesions or normal endometrium, researchers have performed mainly qualitative RT–PCR analysis or immunohistochemistry and have evaluated only total survivin expression (Konno et al., 2000
; Ueda et al., 2002; Goteri et al., 2005). Although Mahotka et al. (2002) and Yamada et al. (2003) measured mRNA expression levels of survivin splice variants using kidney and brain tissue specimens, this is the first successful quantitative analysis of survivin and its isoforms in human endometrium.
Previous studies have indicated that survivin is expressed during fetal development but not in most normal tissues in adults (Ambrosini et al., 1997; Adida et al., 1998; Altieri et al., 1999). In contrast, recent reports have demonstrated survivin expression in normal adult tissues, such as skin, endometrium, endothelial cells, normal blood lymphocytes, pancreas, spleen and colon (Chiodino et al., 1999; Konno et al., 2000; O’Connor et al., 2000; Shinozawa et al., 2000; Hirohashi et al., 2002; O’Driscoll et al., 2003). In their RT–PCR analysis, Hirohashi et al. (2002) reported low levels of survivin expression in all normal tissues tested in adults (stomach, small intestine, large intestine, spleen, lung, kidney, prostate, pancreas, heart and thymus). Yamada et al. (2003) also evaluated gene expression levels of survivin and the two splice variants in brain tissue samples and reported that survivin mRNA was expressed at a very low level in the normal adult brain templates, whereas survivin-2B or survivin-EX3 gene expression was almost undetectable in these specimens. Our present results demonstrated that eutopic endometrium obtained from the patients with or without endometriosis had also lower gene expression levels of survivin, survivin-2B and survivin-EX3 and that mRNA expression levels of the two splice variants were significantly lower than those of survivin. Reduced expression of survivin and its splice variants in normal adult differentiated tissues might be associated with the lower proliferative activity compared with neoplastic lesions (O’Driscoll et al., 2003).
In our study, gene expression levels of survivin in ectopic endometriotic tissues were significantly higher than those in eutopic endometrium obtained from the patients with or without endometriosis over the whole cycle. Interestingly, survivin mRNA expression levels in red peritoneal lesions were higher than those in black lesions. Donnez et al. (1998) suggested that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions, which have higher proliferative activity, can be considered as the first stage of implantation. In contrast, advanced lesions are characteristically blue-black in appearance, which are less active than early lesions (McLaren, 2000). The higher survivin expression in red lesions may provoke an escape from apoptosis and facilitate implantation and viability in the peritoneal cavity. We previously demonstrated using semi-quantitative RT–PCR and immunohistochemical analysis that ectopic endometriotic tissues had higher gene and protein expression levels of survivin compared with normal eutopic endometrium (Ueda et al., 2002). Very recently, Goteri et al. (2005) also indicated that survivin expression is significantly increased in ovarian endometriomata and stated that protection from apoptosis by survivin is closely related to the growth of endometriotic cysts. Moreover, survivin gene and protein expression was closely associated with the reduction of apoptotic cells and invasive phenotype in endometriosis (Ueda et al., 2002). These data strongly suggest that survivin is closely associated with escape from apoptosis of endometriotic tissue and the development of endometriosis.
According to the implantation theory, eutopic endometrium has to have the ability to survive in the peritoneal cavity following retrograde menstruation. Several previous reports (Donnez et al., 1998; McLaren, 2000; Takehara et al., 2004) have indicated that endometriosis may arise from eutopic endometrium which has higher level of angiogenic and proliferative activities in women with endometriosis. However, our present results demonstrated that there was no statistically significant difference in the expression levels of survivin and its splice variants between eutopic endometrium from the patients with endometriosis and that without endometriosis. The up-regulation of survivin gene expression and reduction of apoptosis in endometriotic lesions may be induced possibly by various growth factors and cytokines under the specific environment of peritoneal cavity in women with endometriosis (Gebel et al., 1998; Giudice et al., 1998; Belliard et al., 2004). Apoptosis in human endometrium is also affected by various sex-steroid hormones (Thompson, 1994; Suganuma et al., 1997; Imai et al., 2000; Harada et al., 2004). However, previous reports on the correlation between survivin expression and menstrual cycle are controversial. Konno et al. (2000) reported that survivin protein expression in normal endometrium was strongest in the late-secretary phase, whereas Lehner et al. (2002) demonstrated that survivin gene expression levels were increased in proliferative endometrium. In contrast, our data suggested that no cyclic variation was found in survivin, survivin-2B and survivin-EX3 mRNA expression levels both in ectopic and in eutopic endometrium. Although survivin seems to play an important role in physiological homeostasis in eutopic endometrium (Konno et al., 2000), the cyclic change and the regulatory mechanism of survivin expression during the normal menstrual cycle should be further elucidated.
We finally evaluated the ratio of survivin splice variants/survivin in ectopic and eutopic endometrium to speculate on the functional role of the two splice variants in the pathogenesis of endometriosis. Although there was no significant difference in the ratio of survivin-2B/survivin between ectopic and eutopic endometrium, the ratio of survivin-EX3/survivin in peritoneal endometriotic lesions was significantly higher than that of eutopic endometrium. Mahotka et al. (2002) reported that the ratio of survivin-2B/survivin was significantly decreased in the late tumour stages of renal cell carcinoma, whereas the ratio of survivin-EX3/survivin was not related to the tumour stages. Yamada et al. (2003) demonstrated that the ratio of survivin-EX3/survivin was significantly increased in malignant brain tumours and gliomas compared with non-gliomas, whereas there was no significant difference in the ratio of survivin-2B/survivin in these tumours. Both groups found that the expression patterns of splice variants were dominant for survivin-EX3 in malignant tumours and dominant for survivin-2B in benign tumours. The role of survivin-EX3 is preservation, and the role of survivin-2B is the reduction of the anti-apoptotic property compared with that of survivin (Mahotka et al., 1999). The higher ratio of survivin-EX3/survivin in peritoneal endometriotic lesions may reflect specific biological characteristics of endometriosis more likely as a behaviour of cancer cells. Further studies are needed to clarify the biological role of survivin splice variants in the development of endometriosis.
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Acknowledgements |
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The authors are grateful to several colleagues for collecting clinical materials and K. Sato for her technical assistance. This work was supported in part by High-Tech Research Program of Osaka Medical College.
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References |
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Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J and Altieri DC (1998) Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 152,43–49.[Abstract]
Altieri DC, Marchisio PC and Marchisio C (1999) Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest 79,1327–1333.[Web of Science][Medline]
Ambrosini G, Adida C and Altieri DC (1997) Novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3,917–921.[CrossRef][Web of Science][Medline]
American Society for Reproductive Medicine (1997) Revised American Society for Reproductive Medicine classification of endometriosis. Fertil Steril 67,817–821.[CrossRef][Web of Science][Medline]
Belliard A, Noel A and Foidart JM (2004) Reduction of apoptosis and proliferation in endometriosis. Fertil Steril 82,80–85.[CrossRef][Web of Science][Medline]
Chiodino C, Cesinaro AM, Ottani D, Fantini F, Giannetti A, Trentini GP and Pincelli C (1999) Communication: expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin. J Invest Dermatol 113,415–418.[CrossRef][Web of Science][Medline]
Devereaux QL, Takahashi R, Salvesen GS and Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388,300–304.[CrossRef][Medline]
Donnez J, Smoes P, Gillerot S, Casanas-Roux F and Nisolle M (1998) Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod 13,1686–1690.
Eskenazi B and Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin North Am 24,235–238.[CrossRef][Web of Science][Medline]
Gebel HM, Braun DP, Tambur A, Frame D, Rena N and Dmowski WP (1998) Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis. Fertil Steril 69,1042–1047.[CrossRef][Web of Science][Medline]
Giudice LC, Tazuke SI and Swiersz L (1998) Status of current research on endometriosis. J Reprod Med 43,252–262.[Web of Science][Medline]
Goteri G, Lucarini G, Pieramici T, Filosa A, Pugnaloni A, Montik N, Biagini G, Tranquilli AL, Fabris G, Ciavattini A et al. (2005) Endothelial cell survivin is involved in the growth of ovarian endometriotic cysts. Anticancer Res 25,4313–4318.
Harada T, Kaponis A, Iwabe T, Taniguchi F, Makrydimas G, Sofikitis N, Paschopoulos M, Paraskevaidis E and Terakawa N (2004) Apoptosis in human endometrium and endometriosis. Hum Reprod Update 10,29–38.
Hirohashi Y, Torigoe T, Maeda A, Nabeta Y, Kamiguchi K, Sato T, Yoda J, Ikeda H, Hirata K, Yamanaka N et al. (2002) An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin. Clin Cancer Res 8,1731–1739.
Imai A, Takagi A and Tamaya T (2000) Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometriosis in vitro. Am J Obstet Gynecol 182,1142–1146.[CrossRef][Web of Science][Medline]
Jenkins S, Olive DL and Haney AF (1986) Endometriosis: pathogenetic implication of the anatomic distribution. Obstet Gynecol 67,335–338.[Web of Science][Medline]
Kanda K, Ueda M, Futakuchi H, Yamaguchi H, Mori K, Terai Y and Ueki M (2005) Transcriptional expression of the genes implicated in angiogenesis and tumor invasion in cervical carcinomas. Gynecol Oncol 98,453–461.[CrossRef][Web of Science][Medline]
Konno R, Yamakawa H, Utsunomiya H, Ito K, Sato S and Yajima A (2000) Expression of survivin and Bcl-2 in the normal human endometrium. Mol Hum Reprod 6,529–534.
Lehner R, Enomoto T, McGregor JA, Shroyer L, Haugen BR, Pugazhenthi U and Shroyer KR (2002) Correlation of survivin mRNA detection with histologic diagnosis in normal endometrium and endometrial carcinoma. Acta Obstet Gynecol Scand 81,162–167.[CrossRef][Web of Science][Medline]
Mahotka C, Wenzel M, Springer HE and Gerharz CD (1999) Survivin-
EX3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res 59,6097–6102.
Mahotka C, Krieg T, Krieg A, Wenzel M, Suschek CV, Heydthausen M, Gabbert HE and Gerharz CD (2002) Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas. Int J Cancer 100,30–36.[CrossRef][Web of Science][Medline]
McLaren J (2000) Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update 6,45–55.
O’Connor DS, Schechner JS, Adida C, Mesri M, Rothermel AL, Li F, Nath AK, Pober JS and Altieri DC (2000) Control of apoptosis during angiogenesis by survivin expression in endothelial cells. Am J Pathol 156,393–398.
O’Driscoll L, Linehan R and Clynes M (2003) Survivin: Role in normal cells and in pathological condition. Curr Cancer Drug Targets 3,131–152.[CrossRef][Medline]
Sampson JA (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14,422–469.[Web of Science]
Shinozawa I, Inokuchi K, Wakabayashi I and Dan K (2000) Disturbed expression of the anti-apoptosis gene, survivin, and EPR-1 in hematological malignancies. Leuk Res 24,965–970.[CrossRef][Web of Science][Medline]
Suganuma N, Harada M, Furuhashi M, Nawa A and Kikkawa F (1997) Apoptosis in human endometrial and endometriotic tissues. Horm Res 48,42–47.[CrossRef][Web of Science][Medline]
Takehara M, Ueda M, Yamashita Y, Terai Y, Hung YC and Ueki M (2004) Vascular endothelial growth factor A and C gene expression in endometriosis. Hum Pathol 35,1369–1375.[CrossRef][Web of Science][Medline]
Thompson EB (1994) Apoptosis and steroid hormones. Mol Endocrinol 18,665–673.
Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, Kanda K, Yamaguchi H, Akise D, Hung YC et al. (2002) Survivin gene expression in endometriosis. J Clin Endocrinol Metab 87,3452–3459.
Yamada Y, Kuroiwa T, Nakagawa T, Kajimoto Y, Dohi T, Azuma H, Tsuji M, Kami K and Miyatake S (2003) Transcriptional expression of survivin and its splice variants in brain tumors in humans. J Neurosurg 99,738–745.[Web of Science][Medline]
Submitted on January 30, 2006; resubmitted on March 15, 2006; accepted on March 21, 2006.
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