Premium
Effective intra‐S checkpoint responses to UVC in primary human melanocytes and melanoma cell lines
Author(s) -
CordeiroStone Marila,
McNulty John J.,
Sproul Christopher D.,
Chastain Paul D.,
GibbsFlournoy Eugene,
Zhou Yingchun,
Carson Craig,
Rao Shangbang,
Mitchell David L.,
Simpson Dennis A.,
Thomas Nancy E.,
Ibrahim Joseph G.,
Kaufmann William K.
Publication year - 2016
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12426
Subject(s) - melanoma , dna damage , g2 m dna damage checkpoint , cancer research , neuroblastoma ras viral oncogene homolog , cell culture , melanocyte , biology , cell cycle checkpoint , cell growth , microbiology and biotechnology , cell cycle , cell , chemistry , mutation , dna , genetics , gene , kras
Summary The objective of this study was to assess potential functional attenuation or inactivation of the intra‐S checkpoint during melanoma development. Proliferating cultures of skin melanocytes, fibroblasts, and melanoma cell lines were exposed to increasing fluences of UVC and intra‐S checkpoint responses were quantified. Melanocytes displayed stereotypic intra‐S checkpoint responses to UVC qualitatively and quantitatively equivalent to those previously demonstrated in skin fibroblasts. In comparison with fibroblasts, primary melanocytes displayed reduced UVC‐induced inhibition of DNA strand growth and enhanced degradation of p21Waf1 after UVC, suggestive of enhanced bypass of UVC‐induced DNA photoproducts. All nine melanoma cell lines examined, including those with activating mutations in BRAF or NRAS oncogenes, also displayed proficiency in activation of the intra‐S checkpoint in response to UVC irradiation. The results indicate that bypass of oncogene‐induced senescence during melanoma development was not associated with inactivation of the intra‐S checkpoint response to UVC‐induced DNA replication stress.