p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck.
To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction-singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls) or cisplatin. After injection the tumour volume were measured. The inhibition of tumour growth by cisplatin was defined as the area under the growth curves, and compared with the growth curves of the tumours in the control group. Xenografts with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001) and also tumours with cyclin D1 amplification showed significantly higher resistance (p < 0.001).
Henriksson
Eva
E
Department of Otorhinolaryngology, University Hospital of Malmö, Sweden. Eva.Henriksson@skane.se
Baldetorp
Bo
B
Borg
Ake
A
Kjellen
Elisabeth
E
Akervall
Jan
J
Wennerberg
Johan
J
Wahlberg
Peter
P
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002610:Cheek / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005784:Gene Amplification; D005887:Gingival Neoplasms / Q000188:drug therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy; D009154:Mutation; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D002945:Cisplatin