p53 N-terminal Ser-15 approximately P and Ser-20 approximately P levels in squamous cell lung cancer after radio/chemotherapy.
Functional regulation of p53 protein, a critical regulator of cell cycle and apoptosis, was investigated in fiberoptic bronchoscopy biopsy samples taken from 23 patients suffering from recurrent squamous cell lung cancer by analyzing the expression and phosphorylation status of the p53 at Ser15 and Ser20 before and after treatment with radiotherapy/cisplatin/vinorelbine. Poly(ADP-ribose) levels as a marker of cellular DNA damage, expression of wild-type and mutated p53 protein, and Ki-67 expression as a marker of proliferation was also determined. Median p53 expression increased (61% increase) after therapy. p53 phosphorylated on Ser20 was also increased by approximately 57% in radiotherapy/chemotherapy patients, and these changes correlated with Ki-67 proliferation and with elevated (by 69%; P < 0.01) poly(ADP-ribose) levels. Our data indicate that apart from changes in p53 quantity, post-translational phosphorylation/dephosphorylation-mediated alterations, especially at Ser20 may play a role in p53 stabilization and, therefore, in antiproliferative activity of drugs inducing DNA damage and apoptosis.
Mroz
Robert M
RM
Department of Pneumology, Bialystok Medical University, Bialystok, Poland. robmroz@wp.pl
Holownia
Adam
A
Chyczewska
Elzbieta
E
Chyczewski
Lech
L
Braszko
Jan J
JJ
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004249:DNA Damage; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis; D012044:Regression Analysis; D012694:Serine / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D011064:Poly Adenosine Diphosphate Ribose; D012694:Serine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine