Regulation of gene expression in T-47D human breast cancer cells by progestins and antiprogestins.
The molecular mechanisms by which progestins and antiprogestins inhibit human breast cancer cell growth are essentially unknown. The mechanisms by which they mediate growth inhibition in human breast cancer cells and the expression of the putative autocrine/paracrine growth factors, epidermal growth factor and transforming growth factors alpha and beta-1 were studied under conditions in which progestin and antiprogestin inhibit the growth of T-47D human breast cancer cells in culture. Under the same conditions, the expression of genes such as c-myc, c-jun and c-fos, which are known to have important roles in growth and differentiation, has been measured. The results indicate that progestins and antiprogestins differentially regulate expression of these genes. The data are consistent with the conclusion that the mechanism of growth inhibition of these two agents differs, although an initial interaction with the progesterone receptor is a necessary first step in initiating the as yet ill-defined cascade of events leading to growth inhibition.
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
L C
LC
Murphy
M
M
Alkhalaf
H
H
Dotzlaw
A
A
Coutts
B
B
Haddad-Alkhalaf
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006067:Gonanes / Q000494:pharmacology; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011372:Progestins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006067:Gonanes; D009363:Neoplasm Proteins; D011372:Progestins; D015735:Mifepristone; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D017258:Medroxyprogesterone Acetate; D066246:ErbB Receptors; C053238:onapristone