Mutation of p53 in head and neck squamous cell carcinoma correlates with BCL-2 expression and increased susceptibility to cisplatin-induced apoptosis

摘要: Background. The p53 protein, a well-known tumor suppressor that functions primarily as transcription factor, initiates cell cycle arrest and apoptosis after genotoxic stress. The antiapoptotic regulator Bcl-2 is downstream modulator of p53-induced apoptosis. Loss function the through mutation an important event contributes to cellular transformation. Mutation one most common genetic alterations in squamous carcinomas head neck (SCCHN). We hypothesized associated with expression susceptibility SCCHN. Methods. Exons 5 8 gene were sequenced 22 SCCHN samples correlated rates these tumors. In addition, Bcl-2–expressing line, UMSCC74B, was stably transfected temperature-sensitive mutant construct, levels examined at wild-type temperatures. Results. Bcl-2 inversely status tumors (p = .05). Furthermore, there modest increase (1.7-fold) compared SCCHN. Immunoblotting UMSCC74B cells construct demonstrated shifting temperature (39.5°C) resulted decreased grown (32.5°C). Further investigation showed expressing predominantly more susceptible cisplatin-induced than vector-transfected controls < .0001). Conclusions. These results suggest directly modulates therefore chemotherapy-induced vitro. © 2004 Wiley Periodicals, Inc. Head Neck26: 870–877,