| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular article |
a Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99163-4231
ABSTRACT
Greater than 95% of ovarian cancers originate in the epithelial cells on the surface of the ovary. The current study investigates the expression and action of transforming growth factor alpha (TGF
) in ovarian surface epithelium (OSE) and the underlying stroma in both normal and tumorigenic ovarian tissues. Normal bovine ovaries are used in the current study as a model system to investigate normal OSE functions. Transforming growth factor alpha and its receptor, the epidermal growth factor receptor (EGFR), were detected in the OSE from normal ovaries by immunocytochemistry (ICC). Ovarian stromal tissue also contained reduced but positive TGF and EGFR immunostaining. To examine TGF and EGFR gene expression, RNA was collected from normal bovine OSE and ovarian stromal cells. The TGF and EGFR transcripts were detected in both fresh and cultured OSE and stromal cells by a sensitive quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay. Transforming growth factor alpha gene expression was found to be high in freshly isolated OSE, but low in freshly isolated stroma. In contrast, EGFR expression was higher in the stroma compared to the OSE. Both the ICC and QRT-PCR indicate that normal OSE express high levels of TGF in vivo and in vitro. In vitro, normal ovarian stromal cells develop the capacity to express high levels of EGFR. Human ovarian tumors from stage II, stage III, and stage IV ovarian cancer cases were found to express TGF and EGFR protein in the epithelial cell component of the tumor by ICC analysis. The stromal cell component of human ovarian tumors contained little or no TGF/EGFR immunostaining. Observations suggest that tumor progression may in part require autocrine stimulation of the epithelia. Transforming growth factor alpha was found to stimulate the growth of normal bovine OSE and stroma cells to the same level as epidermal growth factor. Two ovarian cancer cell lines, SKOV3 and OCC1, were also stimulated to proliferate in response to TGF. Transforming growth factor alpha was also found to stimulate the expression of two growth factors previously shown to be produced by OSE. Transforming growth factor alpha stimulates both kit ligand/stem cell factor and keratinocyte growth factor production by OSE. The effect of hormones on TGF and EGFR expression by the OSE was also examined. Human chorionic gonadotropin stimulated TGF expression, but not FSH. Both hCG and FSH stimulated EGFR expression by OSE. Combined observations suggest a role of systemic hormones and a locally produced growth factor, TGF, in OSE biology. Insight is also provided into how the OSE may develop abnormal growth characteristics involved in the onset and progression of ovarian cancer.
First decision: 14 January 2000.
1 This work was supported by a grant from the National Institutes of Health to M.K.S. and a National Cancer Institute Ovarian Cancer Program Project Grant.
2 Correspondence. FAX: 509 335 2176; skinner{at}mail.wsu.edu
3 Current address: Atairgin Technologies, 4 Jenner, Suite 180, Irvine, CA 92618.
This article has been cited by other articles:
|
|
 |
|
  J.-H. Choi, A. S. T. Wong, H.-F. Huang, and P. C. K. Leung Gonadotropins and Ovarian Cancer Endocr. Rev., June 1, 2007; 28(4): 440 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A Margalit, R. G Cowan, R. M Harman, and S. M Quirk Apoptosis of bovine ovarian surface epithelial cells by Fas antigen/Fas ligand signaling Reproduction, November 1, 2005; 130(5): 751 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells Endocr. Relat. Cancer, June 1, 2005; 12(2): 407 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Salamanca, S. L. Maines-Bandiera, P. C. K. Leung, Y.-L. Hu, and N. Auersperg Effects of Epidermal Growth Factor/Hydrocortisone on the Growth and Differentiation of Human Ovarian Surface Epithelium Reproductive Sciences, May 1, 2004; 11(4): 241 - 251. [Abstract] [PDF]
|
|
|
|
 |
|
 E. E. Nilsson and M. K. Skinner Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development Biol Reprod, October 1, 2003; 69(4): 1265 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pribyl, C. B. Muratov, and S. Y. Shvartsman Discrete Models of Autocrine Cell Communication in Epithelial Layers Biophys. J., June 1, 2003; 84(6): 3624 - 3635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pribyl, C. B. Muratov, and S. Y. Shvartsman Long-Range Signal Transmission in Autocrine Relays Biophys. J., February 1, 2003; 84(2): 883 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cardenas, K.A. Burke, R.M. Bigsby, W.F. Pope, and K.P. Nephew Estrogen Receptor {beta} in the Sheep Ovary During the Estrous Cycle and Early Pregnancy Biol Reprod, July 1, 2001; 65(1): 128 - 134. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
