Aromatase expression in ovarian epithelial cancers.
Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal and cancer cells and tissues. Aromatase mRNA expression was analyzed by real-time PCR in ovarian epithelial cancer cell lines, in human ovarian surface epithelial (HOSE) cell primary cultures, and in ovarian tissue specimens (n=94), including normal ovaries, ovarian cysts and cancers. Aromatase mRNA was found to be expressed in HOSE cells, in BG1, PEO4 and PEO14, but not in SKOV3 and NIH:OVCAR-3 ovarian cancer cell lines. Correlation analysis of aromatase expression was performed according to clinical, histological and biological parameters. Aromatase expression in ovarian tissue specimens was higher in normal ovaries and cysts than in cancers (P<0.0001). Using laser capture microdissection in normal postmenopausal ovaries, aromatase was found to be predominantly expressed in epithelial cells as compared to stromal component. Using immunohistochemistry (IHC), aromatase was also detected in the epithelium component. There was an inverse correlation between aromatase and ERalpha expression in ovarian tissues (P<0.001, r=-0.34). In the cancer group, no significant differences in aromatase expression were observed according to tumor histotype, grade, stage and survival. Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERalpha. Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.
Cunat
S
S
Laboratoire de Biologie Cellulaire et Hormonale, Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France. s-cunat@chu-montpellier.fr
Rabenoelina
F
F
Daurès
J-P
JP
Katsaros
D
D
Sasano
H
H
Miller
W R
WR
Maudelonde
T
T
Pujol
P
P
D000730:Androstadienes / Q000494:pharmacology; D001141:Aromatase / Q000032:analysis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003560:Cysts / Q000201:enzymology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D000077289:Letrozole; D042282:Microdissection; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000201:enzymology*; D010053:Ovary / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000730:Androstadienes; D047072:Aromatase Inhibitors; D047628:Estrogen Receptor alpha; D009570:Nitriles; D012333:RNA, Messenger; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase; C056516:exemestane