Inhibition by genistein of prolactin-induced Nb2 lymphoma cell mitogenesis.
Tyrosine kinase activation in mediating the mitogenic action of prolactin (PRL) has been evaluated. Use was made of genistein, a tyrosine kinase antagonist, and cultured rat Nb2 lymphoma cells, i.e. the lactogen-dependent Nb2-11 line and a lactogen-independent subline, Nb2-SFJCD1. Genistein was found to be a potent growth-inhibitor for both lines, inhibiting 3H-thymidine incorporation in Nb2-11 and Nb2-SFJCD1 cells with IC50s of 4.2 and 6.7 micrograms/ml, respectively. Genistein also inhibited expression and translation of the heat shock protein 70 gene and pp40 protein substrate phosphorylation which, in Nb2-11 cells, followed PRL addition within minutes. Genistein inhibition of DNA synthesis in G1-arrested Nb2-11 cells was most pronounced if the agent was added within 1 h of PRL treatment. The results indicate that, while both Nb2 cell lines have a general growth requirement for tyrosyl phosphorylation, the early, PRL-induced tyrosine kinase activation is a component of the PRL mitogenic signal transduction pathway.
Buckley
A R
AR
Department of Pharamcology and Toxicology, University of North Dakota School of Medicine, Grand Forks 58202.
Buckley
D J
DJ
Gout
P W
PW
Liang
H
H
Rao
Y P
YP
Blake
M J
MJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003864:Depression, Chemical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D007529:Isoflavones / Q000494:pharmacology*; D008223:Lymphoma / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D010766:Phosphorylation; D011388:Prolactin / Q000037:antagonists & inhibitors*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006360:Heat-Shock Proteins; D007529:Isoflavones; D009363:Neoplasm Proteins; D011388:Prolactin; D019833:Genistein; D011505:Protein-Tyrosine Kinases