p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis.
Intact p73 function is shown to be an important determinant of cellular sensitivity to anticancer agents. Inhibition of p73 function by dominant-negative proteins or by mutant p53 abrogates apoptosis and cytotoxicity induced by these agents. A polymorphism encoding either arginine (72R) or proline (72P) at codon 72 of p53 influences inhibition of p73 by a range of p53 mutants identified in squamous cancers. Clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants. Polymorphism in p53 may influence individual responsiveness to cancer therapy.
Bergamaschi
Daniele
D
Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St. Mary's Campus, London, England.
Gasco
Milena
M
Hiller
Louise
L
Sullivan
Alexandra
A
Syed
Nelofer
N
Trigiante
Giuseppe
G
Yulug
Isik
I
Merlano
Marco
M
Numico
Gianmauro
G
Comino
Alberto
A
Attard
Marlene
M
Reelfs
Olivier
O
Gusterson
Barry
B
Bell
Alexandra K
AK
Heath
Victoria
V
Tavassoli
Mahvash
M
Farrell
Paul J
PJ
Smith
Paul
P
Lu
Xin
X
Crook
Tim
T
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004358:Drug Therapy; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology*; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins