Inactivated tumor suppressor Rb by nitric oxide promotes mitosis in human breast cancer cells.
Inactivation of tumor suppressor protein retinoblastoma (Rb) is important mechanism for the G1/S transition during cell cycle progression. Human breast cancer cells T47D release great amount of nitric oxide (NO), but its relation to tumor suppressor Rb is unknown. In this study, it is shown that NO induces phosphorylation and inactivation of Rb tumor suppressor protein, increasing G2/M phase and cell proliferation of breast cancer cells T47D. NO did not induce changes in p53 ser-15 phosphorylation, the most phosphorylated site of p53 during its activation. These data indicate that NO induces cell proliferation through the Rb pathway. NO phosphorylates and inactivates tumor suppressor protein Rb inducing mitosis by the p53 independent pathway in breast cancer cell.
Radisavljevic
Ziv
Z
Department of Cancer Cell Biology, Harvard University, School of Public Health, Boston, Massachusetts 02115, USA. zradisav@hsph.harvard.edu
D001120:Arginine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008938:Mitosis; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012694:Serine; D001120:Arginine