Alterations in the p53 pathway and their association with radio- and chemosensitivity in head and neck squamous cell carcinoma.
Chemotherapy and/or radiotherapy are established measures in treatment protocols of head and neck squamous cell carcinoma (HNSCC). However, we still lack reliable predictive markers for the response to radio- and chemotherapy. The p53 pathway is involved in stress response and thus might influence chemo-/radiosensitivity. Using 29 HNSCC cell lines previously characterized for p53 mutations, we simultaneously analyzed several key players in the p53 pathway by RT-PCR, transcript sequencing and immunohistochemistry, and investigated their association with chemosensitivity and radiosensitivity. Cell lines with p53 mutations were slightly more sensitive to cisplatin than those with wild-type p53. The type of mutation did not influence radio- or chemosensitivity. p14(ARF), an activator of p53, was lost or mutated in all cell lines. Three cell lines showed overexpression of HDM-2, a major negative regulator of p53; however, HDM-2 levels did not correlate with radio- or chemosensitivity. HPV-16 oncoproteins were detected in one highly chemoresistant cell line. Our findings suggest that molecular events resulting in the inactivation of the p53 pathway occur in all HNSCC cell lines. However, single alterations in the p53 pathway are not reliable predictors for the response to radio- or chemotherapy in HNSCC.
Hoffmann
Thomas K
TK
Department of Otorhinolaryngology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. tkhoffmann@uni-duesseldorf.de
Sonkoly
Eniko
E
Hauser
Ulrich
U
van Lierop
Anke
A
Whiteside
Theresa L
TL
Klussmann
Jens Peter
JP
Hafner
Dieter
D
Schuler
Patrick
P
Friebe-Hoffmann
Ulrike
U
Scheckenbach
Kathrin
K
Erjala
Kaisa
K
Grénman
Reidar
R
Schipper
Jörg
J
Bier
Henning
H
Balz
Vera
V
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin