IMR Press / FBE / Volume 12 / Issue 2 / DOI: 10.2741/E868

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Deregulation of cell growth and apoptosis in UV-induced melanomagenesis
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1 Department of Biological and Environmental Sciences, College of Arts & Sciences, Qatar University, Doha, Qatar
2 College of Medicine, QU Health, Qatar University, Doha, Qatar
3 Department of Pathology, Stanford University, CA, USA
4 Department of Zoology, Faculty of Sciences, Mansoura University, Al Mansoura, Egypt
5 Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
6 School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Send correspondence to: Allal Ouhtit, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar, Tel: 00974-4403-7572, Fax: 00974-4403-4531, E-mail: aouhtit@qu.edu.qa
Front. Biosci. (Elite Ed) 2020, 12(2), 223–236; https://doi.org/10.2741/E868
Published: 1 March 2020
(This article belongs to the Special Issue Oxidative stress and cardiovascular diseases)
Abstract

We have previously characterized the role of p16/Rb in coordinating the early events in UVB-irradiated skin. As an extension to this work, normal melanocytes and mutant p16-inducible melanoma cell models were employed to elucidate further the coordinated molecular mechanisms occurring during early UVB exposure. Our results showed that melanocytes expressed p16 only at a high UVB dose, with undetectable p53. The Bax/Bcl2 ratio increased at higher dose, indicating that the cells had selected apoptosis program. In the wt-p16 melanoma cells, while low UVB dose upregulated p16, the high dose suppressed it, and further abrogated Cdk6 but not Cdk4. Interestingly, while induction of mutant-p16 increased Cdk4, cdk6 and pRb proteins, UVB exposure did not affect this increase. More interestingly, p16 mutant cells increased their resistance to apoptosis at high UVB-dose, associated with decreased Bax and increased Bcl2 expression. Thus, mutant-p16 appears to dictate a deregulation of cell cycle and increased resistance to apoptosis in melanoma cells. Together, the data indicate a deregulation of p16INK4/Rb pathway as an early event in UVB-induced melanomagenesis.

Keywords
melanoma
p16INK4a/Rb pathway
cell cycle
apoptosis
UVB irradiation.
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