Format

Send to

Choose Destination
Front Biosci (Elite Ed). 2020 Mar 1;12:223-236.

Deregulation of cell growth and apoptosis in UV-induced melanomagenesis.

Author information

1
Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar, aouhtit@qu.edu.qa.
2
Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box 35, PC 123, Al Khoud, Sultanate of Oman.
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.

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.

PMID:
32114459

Supplemental Content

Full text links

Icon for Frontiers in Bioscience
Loading ...
Support Center