TY - JOUR
T1 - Additive roles of XPA and MSH2 genes in UVB-induced skin tumorigenesis in mice
AU - Yoshino, Masafumi
AU - Nakatsu, Yoshimichi
AU - Riele, Hein te
AU - Hirota, Seiichi
AU - Kitamura, Yukihiko
AU - Tanaka, Kiyoji
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, CREST of Japan Science and Technology (JST).
PY - 2002/11/1
Y1 - 2002/11/1
N2 - We have made xeroderma pigmentosum group A gene (XPA)-knockout mice (XPA-/- mice). The XPA-/- mice had no detectable activity for nucleotide excision repair (NER) and showed a high incidence of UVB-induced skin tumorigenesis. We have also found that cell lines derived from skin cancers in UVB-irradiated XPA-/- mice become tolerant to UV-irradiation and showed abnormal UV-induced cell cycle checkpoints and decreased mismatch repair (MMR) activity. These results suggested that the MMR-downregulation may help cells escape killing by UV-irradiation and thus MMR-deficient clones are selected for during the tumorigenic transformation of XPA-/- cells. In this report, we examined whether the incidence of UVB-induced skin tumorigenesis is enhanced in XPA-/-MSH2-/-, XPA-/- and MSH2-/- mice when compared with that in wild-type mice. Our results indicate that the MSH2-deficiency caused a high incidence of spontaneous and UVB-induced skin tumorigenesis and the XPA and MSH2 genes have additive roles in the UV-induced skin tumorigenesis.
AB - We have made xeroderma pigmentosum group A gene (XPA)-knockout mice (XPA-/- mice). The XPA-/- mice had no detectable activity for nucleotide excision repair (NER) and showed a high incidence of UVB-induced skin tumorigenesis. We have also found that cell lines derived from skin cancers in UVB-irradiated XPA-/- mice become tolerant to UV-irradiation and showed abnormal UV-induced cell cycle checkpoints and decreased mismatch repair (MMR) activity. These results suggested that the MMR-downregulation may help cells escape killing by UV-irradiation and thus MMR-deficient clones are selected for during the tumorigenic transformation of XPA-/- cells. In this report, we examined whether the incidence of UVB-induced skin tumorigenesis is enhanced in XPA-/-MSH2-/-, XPA-/- and MSH2-/- mice when compared with that in wild-type mice. Our results indicate that the MSH2-deficiency caused a high incidence of spontaneous and UVB-induced skin tumorigenesis and the XPA and MSH2 genes have additive roles in the UV-induced skin tumorigenesis.
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U2 - 10.1016/S1568-7864(02)00144-1
DO - 10.1016/S1568-7864(02)00144-1
M3 - Article
C2 - 12531021
AN - SCOPUS:0036837133
VL - 1
SP - 935
EP - 940
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 11
ER -
