Lack of Evidence for Aromatase Expression in Human Ovarian Epithelial Carcinoma

Abstract

SUMMARY. It is controversial whether ovarian epithelial carcinoma possesses steroidogenic enzymes. We investigated aromatase expression in ovarian epithelial carcinoma, and compared it with the normal ovary and placenta. Samples were obtained from an ovarian carcinoma cell line SK-OV-3, ovarian tumour tissues from four patients with epithelial carcinoma and one patient with dysgerminoma. Aromatase enzymatic activity was measured in microsome fractions by quantitating 3H 2 0 released from [1-3H] androstenedione and [3H] oestrone converted from [1,2,6,7-3H] androstenedione. Aromatase messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (RT-PCR) using oligonucleotide primers synthesized according to the published human aromatase gene sequence.No aromatase activity was detected in either of two mucinous cystadenocarcinoma specimens or in SK-OV-3 cells, while aromatization proceeded with apparent MichaelisMenten kinetics in the normal ovaries and placentas. The apparent Km value was 200 nmollL for the ovary. Aromatase mRNA was detected in dysgerminoma, and the normal ovary and placenta, but not in any of three mucinous cystadenocarcinoma specimens, one serous cystadenocarcinoma specimen and SK-OV-3 cells. These results for both enzyme activity and gene expression suggest that the human ovarian epithelial carcinoma lacks aromatase. The demonstration of absence of aromatase gene expression raises the possibility that aromatase activity in ovaries bearing epithelial carcinoma may be associated with hyperplastic stromal rather than tumour cells.

Metabolism of Estrogens: Turnover Differs between Platinum-Sensitive and -Resistant High-Grade Serous Ovarian Cancer Cells

“…Conversion of AD to E1 and T to E2 was also not seen in all six cell lines, suggesting no or only very low levels of aromatase (CYP19A1). This is in agreement with the present gene expression analyses and the expression studies by Imai et al [31], which also detected no aromatase in ovarian cancer cell culture and ovarian carcinoma tissue samples. However, in contrast to the cancer cells, aromatase immunoreactivity was observed in stromal cells adjacent to the tumor [32,33].…”

Local estrogen metabolism in epithelial ovarian cancer suggests novel targets for therapy

“…Furthermore, aromatase mRNA expression in OSE was 10,000-fold lower than placental tissue, suggesting that presence of aromatase transcripts in these cells is negligible. Evidence for aromatase expression in EOC and cancer cell lines is more compelling, although not universally demonstrated in all cases or in all studies [32–35] . Interestingly, aromatase expression was noted in stromal cells, but not carcinomatous epithelial cell nests [36] .…”

Effects of levetiracetam and valproate on reproductive endocrine function studied in human ovarian follicular cells

“…The present data confirm an antiestrogenic action of VPA in human granulosa cells, with reduced estradiol secretion and aromatase activity in parallel with increased caspase‐3 activity. This may have clinical implications, particularly for the treatment of different hormone‐dependent tumors (Katsube et al., 1982;Thompson et al., 1988; Koonings et al., 1989; Imai et al., 1994; Kitawaki et al.,1996; Sasano & Harada, 1998; Okubo et al., 2000).…”