In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 85, No. 12 ( 2000-12-01), p. 4889-4899
Abstract:
Ovarian cancer originates mainly from surface epithelial cells, which are potential targets of estrogen action. Using immunohistochemistry and RT-PCR analysis, aromatase (estrogen synthetase) can be detected in human ovarian surface epithelial tumors. In this study, we functionally characterized the aromatase expressed in a primary cell culture, normal human ovarian surface epithelial (HOSE) 17. The apparent Km and Vmax values were determined to be 5.8 ± 0.5 nm, and 0.3 ± 0.0 pmol/mg·h, respectively. The aromatase activity in HOSE 17 cells can be induced effectively by phorbol esters and forskolin, suggesting that estrogen biosynthesis in HOSE 17 cells is mainly regulated through protein kinase C- and protein kinase A-mediated mechanisms. Exon I-specific RT-PCR revealed that phorbol esters predominantly up-regulated promoter II. Whereas forskolin treatment increased exon I.3A-containing messenger RNA, the aromatase activity remained low in the cells treated with this agent. In vitro transcription/translation analysis using plasmids containing T7 promoter and the human snail gene (SnaH) as a reporter capped with different untranslated exon Is revealed that exon PII-containing transcripts were translated more effectively than exon I.3-containing transcripts. These findings explain why aromatase activity is higher in cells with the PII-containing transcripts than is cells with the I.3-containing transcripts. Our results indicate that aromatase is functionally expressed in human ovarian surface epithelial cells and its expression is regulated at both the transcriptional and translational levels.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jcem.85.12.7067
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2000
detail.hit.zdb_id:
2026217-6
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