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

Publication date: Mar 01, 2020

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.

Ouhtit, A., , Gupta, Gaur, R.L., Fernando, A., Abd El-Azim, A.O., and Eid, A. Deregulation of cell growth and apoptosis in UV-induced melanomagenesis. 25982. 2020 Front Biosci (Elite Ed) (12):

Concepts Keywords
Apoptosis Resistance apoptosis melanoma
Bax Branches of biology
Bcl2 Cell biology
Cdk4 Programmed cell death
Cdk6 Cell cycle
Deregulation Proteins
Melanocytes Tumor suppressor genes
Melanoma Oncogenes
Mutant P16
P53 Cyclin-dependent kinase 6
PRb Melanoma
Rb Bcl-2
UV Apoptosis
UVB

Semantics

Type Source Name
pathway KEGG Apoptosis
disease MESH melanoma
pathway KEGG Melanoma
pathway KEGG Cell cycle

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