Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes

被引：55

作者：

Melis, Joost P. M. ^{[1
]}

Wijnhoven, Susan W. P. ^{[1
]}

Beems, Rudolf B. ^{[1
]}

Roodbergen, Marianne ^{[1
]}

van den Berg, Jolanda ^{[1
]}

Moon, Hojin ^{[2
]}

Friedberg, Errol ^{[3
]}

van der Horst, Gijsbertus T. J. ^{[4
]}

Hoeijmakers, Jan H. J. ^{[4
]}

Vijg, Jan ^{[5
]}

van Steeg, Harry ^{[1
]}

机构：

[1] Natl Inst Publ Hlth & Environm, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands

[2] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[4] Erasmus Univ, Med Ctr, MGC Dept Cell Biol & Genet, Ctr Biomed Genet, Rotterdam, Netherlands

[5] Buck Inst Age Res, Novato, CA USA

来源：

CANCER RESEARCH | 2008年 / 68卷 / 05期

关键词：

D O I：

10.1158/0008-5472.CAN-07-6067

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The accumulation of DNA damage is a slow but hazardous phenomenon that may lead to cell death, accelerated aging, and cancer. One of the most versatile defense mechanisms against the accumulation of DNA damage is nucleotide excision repair, in which, among others, the Xeroderma pigmentosum group C (XPC) and group A (XPA) proteins are involved. To elucidate differences in the functions of these two proteins, comprehensive survival studies with Xpa(-/-), Xpc(-/-) and wild-type control female mice in a pure C57BL/6J background were done. The median survival of Xpc(-/-) mice showed a significant decrease, whereas the median survival of Xpa(-/-) mice did not. Strikingly, Xpa(-/-) and Xpc(-/-) mice also showed a phenotypical difference in terms of tumor spectrum. Xpc(-/-) mice displayed a significant increase in lung tumors and a trend toward increased liver tumors compared with Xpa-deficient or wild-type mice. Xpa(-/-) mice showed a significant elevation in liver tumors. Additionally, Xpc-deficient mice exhibited a strong increase in mutant frequency in lung compared with Xpa(-/-) mice, whereas in both models mutant frequency is increased in liver. Our in vitro data displayed an elevated sensitivity to oxygen in Xpc(-/-) in mouse embryonic fibroblasts (MEF) when compared with Xpa(-/-) and wild-type fibroblasts. We believe that XPC plays a role in the removal of oxidative DNA damage and that, therefore, Xpc(-/-) mice display a significant increase in lung tumors and a significant elevation in mutant frequency in lung, and Xpc-deficient MEFs show greater sensitivity to oxygen when compared with Xpa(-/-) and wild-type mice.

引用

页码：1347 / 1353

页数：7

共 49 条

[1] Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population:: a case-control study [J].

Bai, Yun ;

Xu, Liang ;

Yang, Xiaobo ;

Hu, Zhibin ;

Yuan, Jing ;

Wang, Feng ;

Shao, Minhua ;

Yuan, Wentao ;

Qian, Ji ;

Ma, Hongxia ;

Wang, Ying ;

Liu, Hongliang ;

Chen, Weihong ;

Yang, Lin ;

Jing, Guangfu ;

Huo, Xiang ;

Chen, Feng ;

Liu, Yanhong ;

Jin, Li ;

Wei, Qingyi ;

Huang, Wei ;

Shen, Hongbing ;

Lu, Daru ;

Wu, Tangchun .

BMC CANCER, 2007, 7 (1)

[2] Genomic heterogeneity of nucleotide excision repair [J].

Balajee, AS ;

Bohr, VA .

GENE, 2000, 250 (1-2) :15-30

[3]

Berg RJW, 1997, CANCER RES, V57, P581

[4] NUCLEOTIDE EXCISION-REPAIR SYNDROMES - MOLECULAR-BASIS AND CLINICAL SYMPTOMS [J].

BOOTSMA, D ;

WEEDA, G ;

VERMEULEN, W ;

VANVUUREN, H ;

TROELSTRA, C ;

VANDERSPEK, P ;

HOEIJMAKERS, J .

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1995, 347 (1319) :75-81

[5] RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY [J].

BRUGAROLAS, J ;

CHANDRASEKARAN, C ;

GORDON, JI ;

BEACH, D ;

JACKS, T ;

HANNON, GJ .

NATURE, 1995, 377 (6549) :552-557

[6]

Cheo DL, 1999, CANCER RES, V59, P771

[7] Characterization of defective nucleotide excision repair in XPC mutant mice [J].

Cheo, DL ;

Ruven, HJT ;

Meira, LB ;

Hammer, RE ;

Burns, DK ;

Tappe, NJ ;

vanZeeland, AA ;

Mullenders, LHF ;

Friedberg, EC .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1997, 374 (01) :1-9

[8] Cancer in xeroderma pigmentosum and related disorders of DNA repair [J].

Cleaver, JE .

NATURE REVIEWS CANCER, 2005, 5 (07) :564-573

[9] The eukaryotic nucleotide excision repair pathway [J].

Costa, RMA ;

Chiganças, V ;

Galhardo, RD ;

Carvalho, H ;

Menck, CFM .

BIOCHIMIE, 2003, 85 (11) :1083-1099

[10] New functions of XPC in the protection of human skin cells from oxidative damage [J].

D'Errico, Mariarosaria ;

Parlanti, Eleonora ;

Teson, Massimo ;

de Jesus, Bruno M. Bernardes ;

Degan, Paolo ;

Calcagnile, Angelo ;

Jaruga, Pawel ;

Bjoras, Magnar ;

Crescenzi, Marco ;

Pedrini, Antonia M. ;

Egly, Jean-Marc ;

Zambruno, Giovanna ;

Stefanini, Miria ;

Dizdaroglu, Miral ;

Dogliotti, Eugenia .

EMBO JOURNAL, 2006, 25 (18) :4305-4315

← 1 2 3 4 5 →