Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer.
p53 protein is a critical regulator of the cell cycle and apoptosis and its levels and functions change in response to many stimuli. To assess whether the cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53 protein, we determined poly-ADP-ribose levels, the expression of p53 protein and its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radiotherapy and chemotherapy. All 14 patients included in this study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy decreased G2/M cell numbers but increased S-phase cells by almost 50% compared to ploidy status before therapy, while median p53 expression was doubled (109% increase). p53 phosphorylated on Ser-392 was also increased by approximately 70% in patients treated with radiotherapy and with chemotherapy and correlated with elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53 quantity, posttranslational phosphorylation/dephosphorylation-mediated alterations may play an important role in neoplastic cell proliferation as well as in antiproliferative activity of drugs inducing DNA damage and apoptosis.
Holownia
A
A
Department of Clinical Pharmacology, Medical Academy of Bialystok, Bialystok, 15-274 Poland. holow_sinai@hotmail.com
Mroz
R M
RM
Kozlowski
M
M
Chyczewska
E
E
Laudanski
J
J
Chyczewski
L
L
Braszko
J J
JJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011878:Radiotherapy; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D011064:Poly Adenosine Diphosphate Ribose; D012694:Serine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine