Onset of direct 17-beta estradiol effects on proliferation and c-fos expression during oncogenesis of endometrial glandular epithelial cells.
In normal endometrial glandular epithelial cells (GEC), 17beta-estradiol (E2) enhances proliferation and c-fos expression only in the presence of growth factors. On the contrary, growth factors are not required for the E2 effects in cancerous cells. Thus, a repression of E2 action could exist in normal cells and be turned off in cancerous cells, allowing a direct estrogen-dependent proliferation. To verify this hypothesis, we established immortalized and transformed cell models, then investigated alterations of E2 effects during oncogenesis. SV40 large T-antigen was used to generate immortalized GEC model (IGEC). After observation of telomerase reactivation, IGEC model was transfected by activated c-Ha-ras to obtain transformed cell lines (TGEC1 and TGEC2). The phenotypic, morphological, and genetic characteristics of these models were determined before studying the E2 effects. In IGEC, the E2 action on proliferation and c-fos expression required the presence of growth factors, as observed in GECs. In TGECs, this action arose in the absence of growth factors. After IGEC transformation, the activation of ras pathway would substitute the priming events required for the release of repression in GEC and IGEC and thus permit direct E2 effects. Our cell models are particularly suitable to investigate alterations of gene regulation by E2 during oncogenesis.
Nemos
Christophe
C
Laboratoire de Biochimie Biologie Moléculaire, Université de Franche-Comté, U.F.R. Sciences et Techniques, Besançon, France.
Delage-Mourroux
Régis
R
Jouvenot
Michèle
M
Adami
Pascale
P
D000818:Animals; D000957:Antigens, Viral, Tumor; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D016889:Endometrial Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D011905:Genes, ras; D006168:Guinea Pigs; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D000957:Antigens, Viral, Tumor; D016760:Proto-Oncogene Proteins c-fos; D004958:Estradiol