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p53 N-Terminal Ser-15P and Ser-20P Levels in Squamous Cell Lung Cancer after Radio/Chemotherapy

Department of Pneumology, Department of Clinical Pharmacology, and Department of Clinical Molecular Biology, Bialystok Medical University, Bialystok, Poland

Address correspondence to: Dr. Robert Mroz, Department of Pneumology, Bialystok Medical University, Zurawia 14, 15-540 Bialystok, Poland. E-mail: robmroz{at}wp.pl

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 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.

Abbreviations: adenosine diphosphate, ADP • bovine serum albumin, BSA • enhanced chemiluminescence, ECL • ethylenediaminetetraacetic acid, EDTA • gray, Gy • immunoglobulin G antibody, IgG Ab • left lower lobectomy, LLL • left pulmonectomy, LP • murine double minute protein, MDM2 • sodium vanadate, Na₃VO₄ • sodium azide, NaN₃ • saponine NP-40, NP-40 • p53 protein, p53 • p53 phosphorylated on serines 15, 20, 392, Ser15P, Ser20P, Ser392P • p300 protein, p300 • phenylmethylsulfonyl fluoride, PMSF • phosphate-buffered saline + Tween, PBS-T • poly(ADP-ribose), PAR • proliferation-associated nuclear antigen Ki-67, Ki-67 • right lower bilobectomy, RLB • right pulmonectomy, RP • right upper lobectomy, RUL • sodium dodecyl sulfate polyacrylamide gel electrophoresis, SDS-PAGE • tumor, node, metastasis, TNM • Western blot, WB

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