Molecular Human Reproduction, Vol. 8, No. 8, 734-741,
August 2002
© 2002 European Society of Human Reproduction and Embryology
Ovary and oogenesis |
The soluble and membrane-anchored forms of heparin-binding epidermal growth factor-like growth factor appear to play opposing roles in the survival and apoptosis of human luteinized granulosa cells
Department of Obstetrics and Gynecology, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa, Japan 078-8510
This study aims to investigate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its role in regulating apoptosis of human luteinized granulosa cells (LGC). By using RT–PCR and immunocytochemistry, the expression of HB-EGF and the EGF receptor family was demonstrated. HER4, one of the two cognate receptors for HB-EGF, was found translocated into the nucleus. HB-EGF exists in two forms, the precursor membrane-anchored form and the mature secreted form. Addition of recombinant HB-EGF, which acts as the secreted form, into the cell culture inhibited apoptosis and appeared to stimulate mitosis, indicating that the secreted form is potentially an anti-apoptotic factor and a mitogen for LGC. In contrast, CRM197, a specific inhibitor for the interaction between HB-EGF and the EGF receptor, inhibited rather than enhanced apoptosis, suggesting that the membrane-anchored form constitutively functions as a pro-apoptotic factor for LGC. Furthermore, the finding that apoptosis inhibition by CRM197 in the aggregate cells was much more pronounced than in the single cells indicates that pro-apoptotic activity was carried out in a juxtacrine fashion, as would be expected for the membrane-anchored form of HB-EGF. These data suggest that HB-EGF may be a unique regulator of LGC apoptosis, with two functionally opposing products arising from the same gene.
apoptosis/EGF receptor family/HB-EGF/luteinized granulosa cells
1 To whom correspondence should be addressed. E-mail: pan{at}mail.asahikawa-med.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Seo, M.-J. Lee, J. H. Heo, Y.-I. Lee, Y. Kim, S.-Y. Kim, E.-S. Lee, and Y.-S. Juhnn G Protein beta{gamma} Subunits Augment UVB-induced Apoptosis by Stimulating the Release of Soluble Heparin-binding Epidermal Growth Factor from Human Keratinocytes J. Biol. Chem., August 24, 2007; 282(34): 24720 - 24730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, J. Li, C. Ying Wang, A. H. Yan Kwok, and F. C. Leung Epidermal Growth Factor (EGF) Receptor Ligands in the Chicken Ovary: I. Evidence for Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Potential Oocyte-Derived Signal to Control Granulosa Cell Proliferation and HB-EGF and Kit Ligand Expression Endocrinology, July 1, 2007; 148(7): 3426 - 3440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Akayama, S. Takekida, N. Ohara, H. Tateiwa, W. Chen, K. Nakabayashi, and T. Maruo Gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor and human epidermal growth factor receptors in human corpus luteum Hum. Reprod., October 1, 2005; 20(10): 2708 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Hinkle, S. W. Sunnarborg, D. Loiselle, C. E. Parker, M. Stevenson, W. E. Russell, and D. C. Lee Selective Roles for Tumor Necrosis Factor {alpha}-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family: THE JUXTAMEMBRANE STALK DETERMINES CLEAVAGE EFFICIENCY J. Biol. Chem., June 4, 2004; 279(23): 24179 - 24188. [Abstract] [Full Text] [PDF]
|
|