Tamoxifen inhibits prolactin signal transduction in ER - NOG-8 mammary epithelial cells.
Tamoxifen (TAM), an antiestrogen, also acts as an antilactogen in mammary cells. In the present study we analyze the effect of TAM on the signal transduction pathway for prolactin (Prl). TAM bound specifically to NOG-8, an estrogen receptor-negative mammary cell line. Within 5 min of Prl treatment, raf-1, MEK and MAP kinase were induced 2-3-fold over the control level. TAM completely inhibited this Prl-induced activation of kinases as well as Prl binding and cell growth. These results indicate the potential role of TAM as an antilactogen in Prl responsive systems.
Das
R
R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892-1402, USA.barbarav@helix.nih.gov
Vonderhaar
B K
BK
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D048369:MAP Kinase Kinase 1; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011960:Receptors, Estrogen / Q000172:deficiency / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013629:Tamoxifen / Q000378:metabolism / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases