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Comparison of UVB and UVC Effects on the DNA Damage‐Response Protein 53BP1 in Human Pancreatic Cancer
Author(s) -
Uehara Fuminari,
Miwa Shinji,
Tome Yasunori,
Hiroshima Yukihiko,
Yano Shuya,
Yamamoto Mako,
Efimova Elena,
Matsumoto Yasunori,
Maehara Hiroki,
Bouvet Michael,
Kanaya Fuminori,
Hoffman Robert M.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24837
Subject(s) - green fluorescent protein , clonogenic assay , microbiology and biotechnology , chemistry , pancreatic cancer , dna damage , cancer research , cell culture , in vitro , dna , biology , cancer , biochemistry , genetics , gene
We have previously demonstrated that ultraviolet (UV) light is effective against a variety of cancer cells expressing fluorescent proteins in vivo as well as in vitro. In the present report, we compared the DNA damage repair (DDR) response of pancreatic cancer cells after UVB or UVC irradiation. The UV‐induced DNA damage repair was imaged with green fluorescent protein (GFP) fused to the DDR‐related chromatin‐binding protein 53BP1 in MiaPaCa‐2 human pancreatic cancer cells growing in 3D Gelfoam® histoculture and in superficial tumors grown in nude mice. 53BP1‐GFP forms foci during DNA damage repair. A clonogenic assay in 2D monolayer culture initially showed that UVC and UVB inhibited MiaPaCa‐2 cell proliferation in a dose‐dependent manner, with UVC having more efficacy. Three‐dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1‐GFP foci to be observed within 1 h after UV irradiation, indicating the onset of DDR response. UVB‐induced 53BP1‐GFP focus formation was observed up to a depth of 120 µm in MiaPaCa‐2 cells on Gelfoam® compared to 80 µm for UVC. UVB‐induced 53BP1‐GFP focus formation was observed up to a depth of 80 µm in MiaPaCa‐2 cells, implanted within skin flaps in mice, at a significantly greater extent than UVC. MiaPaCa‐2 cells irradiated by UVB or UVC in the skin‐flap mouse model had a significant decrease in tumor growth compared to untreated controls with UVB having more efficacy than UVC. Our results demonstrate that UVB has greater tissue penetration than UVC because of its longer wavelength and has clinical potential for eradicating superficial cancer. J. Cell. Biochem. 115: 1724–1728, 2014. © 2014 Wiley Periodicals, Inc.