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

Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar,
Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box 35, PC 123, Al Khoud, Sultanate of Oman.
Department of Pathology, Stanford University, CA, USA.
Department of Zoology, Faculty of Sciences, Mansoura University, Al Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.


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.


Supplemental Content

Full text links

Icon for Frontiers in Bioscience
Loading ...
Support Center