TY - JOUR
T1 - Bone morphogenetic protein-2 induces cyclin kinase inhibitor p21 and hypophosphorylation of retinoblastoma protein in estradiol-treated MCF-7 human breast cancer cells
AU - Ghosh-Choudhury, Nandini
AU - Ghosh-Choudhury, Goutam
AU - Celeste, Anthony
AU - Ghosh, Paramita M.
AU - Moyer, Marissa
AU - Abboud, Sherry L.
AU - Kreisberg, Jeffrey
N1 - Funding Information:
We thank Dr. Robert Klebe for his kind gift of MCF-7 breast cancer cells and Dr. Dan Riley for critical reading of the manuscript. This work was supported by the Department of Defense Idea Grant DAMD17-99-1-9400 awarded to N.G.-C. G.G.C. is supported by a Department of Veterans Affairs Medical Research Service grant and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-50190. N.G.-C. is a recipient of an institutional American Cancer Society grant.
PY - 2000/7/21
Y1 - 2000/7/21
N2 - The biologic effects and mechanisms by which bone morphogenetic proteins (BMPs) function in breast cancer cells are not well defined. A member of this family of growth and differentiation factors, BMP-2, inhibited both basal and estradiol-induced growth of MCF-7 breast tumor cells in culture. Flow cytometric analysis showed that in the presence of BMP-2, 62% and 45% of estradiol-stimulated MCF-7 cells progressed to S-phase at 24 h and 48 h, respectively. Estradiol mediates growth of human breast cancer cells by stimulating cyclins and cyclin-dependent kinases (CDKs). BMP-2 significantly increased the level of the cyclin kinase inhibitor, p21, which in turn associated with and inactivated cyclin D1. BMP-2 inhibited estradiol-induced cyclin D1-associated kinase activity. Also estradiol-induced CDK2 activity was inhibited by BMP-2. This inhibition of CDK activity resulted in hypophosphorylation of retinoblastoma protein thus keeping it in its active form. These data provide the first evidence by which BMP-2 inhibits estradiol-induced proliferation of human breast cancer cells. (C) 2000 Elsevier Science B.V.
AB - The biologic effects and mechanisms by which bone morphogenetic proteins (BMPs) function in breast cancer cells are not well defined. A member of this family of growth and differentiation factors, BMP-2, inhibited both basal and estradiol-induced growth of MCF-7 breast tumor cells in culture. Flow cytometric analysis showed that in the presence of BMP-2, 62% and 45% of estradiol-stimulated MCF-7 cells progressed to S-phase at 24 h and 48 h, respectively. Estradiol mediates growth of human breast cancer cells by stimulating cyclins and cyclin-dependent kinases (CDKs). BMP-2 significantly increased the level of the cyclin kinase inhibitor, p21, which in turn associated with and inactivated cyclin D1. BMP-2 inhibited estradiol-induced cyclin D1-associated kinase activity. Also estradiol-induced CDK2 activity was inhibited by BMP-2. This inhibition of CDK activity resulted in hypophosphorylation of retinoblastoma protein thus keeping it in its active form. These data provide the first evidence by which BMP-2 inhibits estradiol-induced proliferation of human breast cancer cells. (C) 2000 Elsevier Science B.V.
KW - BMP-2
KW - Breast cancer cell
KW - p21
KW - pRb
UR - http://www.scopus.com/inward/record.url?scp=0034698099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034698099&partnerID=8YFLogxK
U2 - 10.1016/S0167-4889(00)00060-4
DO - 10.1016/S0167-4889(00)00060-4
M3 - Article
C2 - 10903423
AN - SCOPUS:0034698099
VL - 1497
SP - 186
EP - 196
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 2
ER -