In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 85, No. 12 ( 2000-12-01), p. 4889-4899
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jcem.85.12.7067
Sprache:
Englisch
Verlag:
The Endocrine Society
Publikationsdatum:
2000
ZDB Id:
2026217-6
Bookmarklink
