Early ultraviolet B-induced G1 arrest and suppression of the malignant phenotype by wild-type p53 in human squamous cell carcinoma cells

Experimental Cell Research
S J CourtoisMarjan Garmyn

Abstract

Wild-type p53 (wt-p53) negatively controls cell cycle progression after cellular stress mediating either a temporary growth arrest or apoptosis, depending on the cell type and nature of the cellular stress. The aberrant proliferation which is characteristic of tumor cells may be suppressed by exogenous wt-p53 and appears to depend strongly on the level of reexpression. We performed retroviral-mediated gene transfer of wt-p53 into a human squamous cell carcinoma cell line from the head and neck region (A253 cell line) lacking endogenous p53. This allowed us to study the effect of wt-p53 on the malignant phenotype and on the response to the DNA damaging agent ultraviolet B (UVB). Restoration of wt-p53 in malignant keratinocytes suppressed tumorigenicity in nude mice although p53-reconstituted cells eventually formed small tumors with long latency. Cells derived from these tumors showed reduced expression of wt-p53. Exogenous wt-p53 increased baseline mRNA expression of the small proline rich proteins 1 and 2, consistent with a prodifferentiating effect. After exposure to a biological UVB dose, only p53-positive A253 cells underwent an early and transient G1 arrest. Both p53-positive and -negative A253 cells displayed a late G2 de...Continue Reading

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Citations

May 3, 2007·Biological & Pharmaceutical Bulletin·Takahiro Ishida, Ikuyo Sakaguchi
Jan 14, 2010·Connective Tissue Research·Ines DammakHamadi Attia
Apr 16, 2010·The Journal of Investigative Dermatology·Kris NysPatrizia Agostinis
Nov 17, 2001·The Journal of Investigative Dermatology·M GarmynD Maes
Nov 9, 2000·The Journal of Investigative Dermatology·C FumelliC Pincelli
Jun 12, 2004·The Journal of Investigative Dermatology·David DecraeneMarjan Garmyn
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Dec 25, 2002·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·Wendy C Weinberg, Mitchell F Denning
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Jan 24, 2007·Molecular Cancer Therapeutics·Joshua L FischerMartin L Smith
May 26, 1998·Biochemical and Biophysical Research Communications·S J CourtoisM Garmyn

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