Aromatase expression in ovarian epithelial cancers |
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| Authors: | Cunat S Rabenoelina F Daurès J-P Katsaros D Sasano H Miller W R Maudelonde T Pujol P |
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| Institution: | 1. Department of Cell Biology and Biophysics, Faculty of Biology, NKUA, Greece;2. Chronic Hemodialysis Centre “Ionion”, Piraeus, Greece;3. Laboratory of Hematology and Transfusion Medicine, Department of Medical Laboratories, Faculty of Health and Caring Professions, Technological and Educational Institute of Athens, Greece;1. Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden;2. Stockholm Gerontology Research Center, Stockholm, Sweden;3. Karolinska University Hospital, Stockholm, Sweden;1. Consorci d''Atenció Primària de Salut Eixample (CAPSE), Grup Transversal de Recerca en Atenció Primària, Institut d''Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain;2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain;3. Lipid Clinic, Department of Endocrinology and Nutrition, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain;4. Diagnostic Imaging Centre, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain |
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| Abstract: | 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. |
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