Please use this identifier to cite or link to this item: https://doi.org/10.1158/1078-0432.CCR-07-1422
Title: Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin
Authors: Avery-Kiejda, K.A
Xu, D.Z
Adams, L.J
Scott, R.J
Vojtesek, B
Lane, D.P 
Hersey, P
Keywords: cisplatin
delta40p53 protein
isoprotein
messenger RNA
p21 activated kinase
protein p53
protein p53beta
unclassified drug
alpha chain
article
cancer cell culture
cellular distribution
fibroblast
human
human cell
melanocyte
melanoma cell
molecular weight
priority journal
protein expression
reverse transcription polymerase chain reaction
two dimensional electrophoresis
Western blotting
Antineoplastic Agents
Cisplatin
DNA Damage
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Melanoma
Molecular Weight
Protein Isoforms
Tumor Cells, Cultured
Tumor Suppressor Protein p53
Up-Regulation
Issue Date: 2008
Citation: Avery-Kiejda, K.A, Xu, D.Z, Adams, L.J, Scott, R.J, Vojtesek, B, Lane, D.P, Hersey, P (2008). Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin. Clinical Cancer Research 14 (6) : 1659-1668. ScholarBank@NUS Repository. https://doi.org/10.1158/1078-0432.CCR-07-1422
Rights: Attribution 4.0 International
Abstract: Purpose: Metastatic melanoma is largely unresponsive to DNA-damaging chemotherapy agents, although WT p53 is frequently detected. Several isoforms of p53 have been discovered, some of which inhibit p53 function. We therefore examined whether p53 isoforms were present in melanoma and whether they may contribute to aberrant p53 function in melanoma. Experimental Design: We studied the expression and subcellular localization of p53 and its isoforms in a panel of human melanoma cell lines using Western blot, two-dimensional electrophoresis, and reverse transcription-PCR. We also characterized the relationship between the expression of p53, p53 isoforms, and p53 target genes following treatment with the DNA damaging agent cisplatin. Results: We report that p53? and ?40p53 were expressed in themajority ofmelanoma cell lines at the mRNA level, but were absent or expressed at low levels in fibroblasts and melanocytes, suggesting that their expression may play a role in melanoma development. Analysis by two dimensional gel electrophoresis revealed that p53? was expressed at the protein level in melanoma cells. Both p53 and the small molecular weight forms of p53 were aberrantly expressed between the nuclear and cytosolic fractions of melanoma cell lines, compared with normal fibroblasts. Treatment with cisplatin had differential effects on WTp53 and the small molecular weight form of p53 that were cell line dependent. ?40p53 was shown to inhibit, whereas p53? was shown to enhance, p53-dependent transcription of p21 and PUMA. Conclusions: p53? and ?40p53 are expressed in melanoma and this may have important implications for understanding resistance of melanoma to DNA-damaging chemotherapy. © 2008 American Association for Cancer Research.
Source Title: Clinical Cancer Research
URI: https://scholarbank.nus.edu.sg/handle/10635/181024
ISSN: 1078-0432
DOI: 10.1158/1078-0432.CCR-07-1422
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1158_1078-0432_CCR-07-1422.pdf520.68 kBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons