Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer1
| Autor: | Michael K. Skinner, Vinayak Doraiswamy, Jeff A. Parrott |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
endocrine system
medicine.medical_specialty TGF alpha Stromal cell Growth factor medicine.medical_treatment Cell Biology General Medicine Biology medicine.disease chemistry.chemical_compound Endocrinology Reproductive Medicine chemistry Epidermal growth factor Internal medicine medicine Cancer research biology.protein Keratinocyte growth factor Epidermal growth factor receptor Ovarian cancer Autocrine signalling |
| Zdroj: | Biology of Reproduction. 63:789-796 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod63.3.789 |
| Popis: | 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 (TGFa) 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 TGFa and EGFR immunostaining. To examine TGFa and EGFR gene expression, RNA was collected from normal bovine OSE and ovarian stromal cells. The TGFa 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 TGFa 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 TGFa 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 TGFa/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 TGFa. 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 TGFa and EGFR expression by the OSE was also examined. Human chorionic gonadotropin stimulated TGFa 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, TGFa, in OSE biology. Insight is also provided into how the OSE may develop abnormal growth char1This 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. |
| Databáze: | OpenAIRE |
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