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.
Original language | English |
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Pages (from-to) | 223-236 |
Number of pages | 14 |
Journal | Frontiers in Bioscience - Elite |
Volume | 12 |
Issue number | 2 |
DOIs | |
Publication status | Published - Mar 1 2020 |
Externally published | Yes |
Keywords
- Apoptosis
- Cell cycle
- Melanoma
- P16INK4a/Rb pathway
- UVB irradiation
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology