Tamoxifen-induced growth arrest and apoptosis in pituitary tumor cells in vitro via a protein kinase C-independent pathway.
Protein kinase C (PKC), a kinase family involved in cell signal transduction, is overexpressed in most pituitary adenoma cells. We studied the effect of tamoxifen, an estrogen receptor antagonist and also a protein kinase inhibitor, on pituitary tumor cell proliferation and the induction of apoptosis; and we compared its effects with those of another PKC inhibitor, staurosporine. Tamoxifen induced growth arrest and apoptosis in a mouse pituitary adenoma cell line, AtT20, and in low-passage human primary pituitary tumor cell cultures. Staurosporine also inhibited pituitary tumor cell growth. PKC activity in AtT20 cells was inhibited by staurosporine and by prolonged treatment with phorbol myristate acetate, which down-regulates PKC activity, but not by tamoxifen, at the dosages used to induce apoptosis. Our findings suggest that tamoxifen induces apoptosis in AtT20 cells independent of a classical PKC isozyme pathway.
Simard
Marie
M
Department of Neurosurgery, New York Medical College, Valhalla, NY, USA.
Zhang
Wei
W
Hinton
David R
DR
Chen
Thomas C
TC
Weiss
Martin H
MH
Su
Yu-Zhuang
YZ
Gopalakrishna
Rayadu
R
Law
Ronald E
RE
Couldwell
William T
WT
D000236:Adenoma / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D013629:Tamoxifen; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate