Characterization of estrogen-dependent growth of cultured MCF-7 human breast-cancer cells expressing 17beta-hydroxysteroid dehydrogenase type 1.
17beta-hydroxysteroid dehydrogenase (17HSD) type I converts the weakly active estrogen, estrone, into highly active estradiol. In addition to being essential for gonadal estradiol biosynthesis, the enzyme is also expressed in a significant proportion of breast tumors. In order to study the role of the enzyme in estrogen-dependent growth of breast cancer, MCF-7 breast-cancer cells stably expressing human 17HSD type I were generated. In control MCF-7 cells a very low 17HSD activity was observed and, in line with its low estrogenic activity, estrone was devoid of the growth-enhancing effect of estradiol. The presence of the enzyme in the stably transfected MCF-7 cells resulted in a rapid conversion of estrone into estradiol but did not alter the estrogen-receptor concentration in the cells. However, in transfected cells, estrone had a growth-promoting effect practically identical to that of estradiol. The presence or absence of 17HSD type I in breast-cancer cells may therefore be decisive with regard to estrogen exposure and the estrogen-responsive growth of breast-cancer tissues.
Miettinen
M M
MM
Biocenter Oulu, Department of Clinical Chemistry, University of Oulu, Finland.
Poutanen
M H
MH
Vihko
R K
RK
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004967:Estrogens; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase