Deregulation of cell growth and apoptosis in UV-induced melanomagenesis

Allal Ouhtit*, Ishita Gupta, Rajiv L. Gaur, Augusta Fernando, Amira O. Abd El-Azim, Ali Eid, Therese M. Becker

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)223-236
Number of pages14
JournalFrontiers in Bioscience - Elite
Volume12
Issue number2
DOIs
Publication statusPublished - Mar 1 2020
Externally publishedYes

Keywords

  • Apoptosis
  • Cell cycle
  • Melanoma
  • P16INK4a/Rb pathway
  • UVB irradiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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