DeltaNp63alpha levels correlate with clinical tumor response to cisplatin.
After exposure to damaging agents, the p53 tumor suppressor is stabilized mediating cell cycle arrest and apoptosis. p53 family member, DeltaNp63 promotes cell proliferation and accelerates tumor growth. We previously found that the genotoxic stress agents induced a decrease of DeltaNp63alpha. We further observed that genotoxic stress mediated phosphorylation of DeltaNp63alpha targeting it into proteasome degradation. Here, we found that high DeltaNp63 protein levels in primary tumors accurately predicted response to platinum based chemotherapy and a favorable outcome in head and neck cancer patients. Our data suggest that degradation of DeltaNp63alpha is part of the cellular response to DNA damage in head and neck cancers. The findings may have implications for the rational use of DNA damaging agents in human cancer.
Zangen
Rachel
R
Department of Otolaryngology/Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ratovitski
Edward
E
Sidransky
David
D
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D021122:Protein Subunits; D025521:Tumor Suppressor Proteins; D002945:Cisplatin