Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information.

p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers.

Sang M, Li Y, Ozaki T, Ono S, Ando K, Yamamoto H, Koda T, Geng C, Nakagawara A

Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.

It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated in response to adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in turn, stabilized p73. Luciferase reporter analysis and colony formation assays demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated transcriptional activity as well as its pro-apoptotic function. Furthermore, enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436 cells. Taken together, our present results strongly suggest that p73-dependent induction of 14-3-3sigma plays an important role in the regulation of chemo-sensitivity of breast cancers bearing p53 mutation.

Published 11 July 2006 in Biochem Biophys Res Commun, 347(1): 327-33.
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