[en] The rat is considered an excellent model for studying human breast cancer. Therefore, understanding the genetic basis of susceptibility to mammary cancer in this species is of great interest. Previous studies based on crosses involving the susceptible strain WF (crossed with the resistant strains COP or WKY) and focusing on tumor multiplicity as the susceptibility phenotype led to the identification of several loci that control chemically induced mammary cancer. The present study was aimed to determine whether other loci can be identified by analyzing crosses derived from another susceptible strain on the one hand, and by including phenotypes other than tumor multiplicity on the other hand. A backcross was generated between the susceptible SPRD-Cu3 strain and the resistant WKY strain. Female progeny were genotyped with microsatellite markers covering all rat autosomes, treated with a single dose of DMBA, and phenotyped with respect to tumor latency, tumor multiplicity, and tumor aggressiveness. Seven loci controlling mammary tumor development were detected. Different loci control tumor multiplicity, latency, and aggressiveness. While some of these loci colocalize with loci identified in crosses involving the susceptible strain WF, new loci have been uncovered, indicating that the use of distinct susceptible and resistant strain pairs will help in establishing a comprehensive inventory of mammary cancer susceptibility loci
Disciplines :
Genetics & genetic processes Oncology
Author, co-author :
Quan, X.
Laes, Jean-François
Stieber, D.
Rivière, M.
Russo, J.
Wedekind, D.
Coppieters, Wouter ; Université de Liège - ULiège > Département de productions animales > Département de productions animales
Farnir, Frédéric ; Université de Liège - ULiège > Département de productions animales > Biostatistique, économie, sélection animale
Georges, Michel ; Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Szpirer, J.
Szpirer, C.
Language :
English
Title :
Genetic identification of distinct loci controlling mammary tumor multiplicity, latency and aggressiveness in the rat
Publication date :
April 2006
Journal title :
Mammalian Genome
ISSN :
0938-8990
eISSN :
1432-1777
Publisher :
Springer Verlag, New York, United States - New York
Balmain A, Nagase H (1998) Cancer resistance genes in mice: models for the study of tumour modifiers. Trends Genet 14, 139-144
Churchill GA, Doerge R (1995) Empirical values for quantitative trait mapping. Genetics 138, 963-971
Claus EB, Schildkraut JM, Thompson WD, Risch NJ (1996) The genetic attributable risk of breast and ovarian cancer. Cancer 77, 2318-2324
Claus EB, Schildkraut J, Iversen ES Jr, Berry D, Parmigiani G (1998) Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history. J Natl Cancer Inst 90, 1824-1829
Coppieters W, Kvasz A, Farnir F, Arranz JJ, Grisart B, et al. (1998) A rank-based nonparametric method for mapping quantitative trait loci in outbred half-sib pedigrees: application to milk production in a granddaughter design. Genetics 149, 1547-1555
Dahlman I, Eaves IA, Kosoy R, Morrison VA, Heward J, et al. (2002) Parameters for reliable results in genetic association studies in common diseases. Nat Genet 30, 149-150
Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, et al. (1994) BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120-122
Gould KA, Tochacek M, Schaffer BS, Reindl TM, Murrin CR, et al. (2004) Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: mapping of Emca1 and Emca2 to chromosomes 5 and 18. Genetics 168, 2113-2125
Gould MN (1986) Inheritance and site of expression of genes controlling susceptibility to mammary cancer in an inbred rat model. Cancer Res 46, 1199-1202
Gould MN (1993) Cellular and molecular aspects of the multistage progression of mammary carcinogenesis in humans and rats.. Semin Cancer Biol 4, 161-169
Gould MN (1995) Rodent models for the study of etiology, prevention and treatment of breast cancer. Semin Cancer Biol 6, 147-152
Greenhouse DD, Festing MFW, Hasan S, Chen AL (1990) Catalogue of inbred strains of rats. In Hedrich HHJ, ed. Genetic Monitoring of Inbred Strains of Rats, (New York: Gustav Fischer Verlag Press), pp 410-486
Haag JD, Newton MA, Gould MN (1992) Mammary carcinoma suppressor and susceptibility genes in the Wistar-Kyoto rat. Carcinogenesis 13, 1933-1935
Helou K, Lu XC, Montelius-Alatalo K, Ståhl F, Klinga-Levan K, et al. (2000) A dual-color FISH framework map for the characterization of the Sail tumor suppression region on rat chromosome 5. Genes Chromosomes Cancer 27, 362-372
Hsu LC, Kennan WS, Shepel LA, Jacob HJ, Szpirer C, et al. (1994) Genetic identification of Mcs-1, a rat mammary carcinoma suppressor gene. Cancer Res 54, 2765-2770
Huggins CB, Ueda N, Wiessler M (1981) N-Nitroso-N-methylurea elicits mammary cancer in resistant and sensitive rat strains. Proc Natl Acad Sci. USA 78, 1185-1188
Isaacs JT (1986) Genetic control of resistance to chemically induced mammary adenocarcinogenesis in the rat. Cancer Res 46, 3958-3963
Isaacs JT (1988) Inheritance of a genetic factor from the Copenhagen rat and the suppression of chemically induced mammary adenocarcinogenesis. Cancer Res 48, 2204-2213
Islam MQ, Szpirer J, Szpirer C, Islam K, Dasnoy JF, et al. (1989) A gene for the suppression of anchorage independence is located in rat chromosome 5 bands q22-23, and the rat alpha-interferon locus maps to the same region. J Cell Sci 92, 147-162
Kindler-Röhrborn A, Kölsch BU, Fischer C, Held S, Rajewsky MF (1999) Ethylnitrosourea-induced development of malignant schwannomas in the rat: two distinct loci on chromosome 10 involved in tumor susceptibility and oncogenesis. Cancer Res 59, 1109-1114
Korkola JE, Archer MC (1999) Resistance to mammary tumorigenesis in Copenhagen rats is associated with the loss of preneoplastic lesions. Carcinogenesis 20, 221-227
Kruglyak L, Lander ES (1995a) A nonparametric approach for mapping quantitative trait loci. Genetics 139, 1421-1428
Kruglyak L, Lander ES (1995b) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11, 241-247
Kruglyak L, Lander ES (1995c) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57, 439-454
Lan H, Kendziorski CM, Haag JD, Shepel LA, Newton MA, et al. (2001) Genetic loci controlling breast cancer susceptibility in the Wistar-Kyoto rat. Genetics 157, 331-339
Lancaster M, Rouse J, Hunter KW (2005) Modifiers of mammary tumor progression and metastasis on mouse Chromosomes 7, 9, and 17. Mamm Genome 16, 120-126
Lander ES, Green P (1987) Construction of multilocus genetic linkage maps in humans.. Proc Natl Acad Sci USA 84, 2363-2367
Le Voyer T, Lu Z, Babb J, Lifsted T, Williams M, et al. (2000) An epistatic interaction controls the latency of a transgene-induced mammary tumor. Mamm Genome 11, 883-889
Le Voyer T, Rouse J, Lu Z, Lifsted T, Williams M, et al. (2001) Three loci modify growth of a transgene-induced mammary tumor: suppression of proliferation associated with decrease microvessel density. Genomics 74, 253-261
Martin AM, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 92, 1126-1135
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, et al. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 26, 66-71
Nathanson KL, Weber BL (2001) "Other" breast cancer susceptibility genes: searching for more holy grail. Hum Mol Genet 10, 715-720
Nilsson S, Helou K, Walentinsson A, Szpirer C, Nerman O, et al. (2001) Rat-mouse and rat-human comparative maps based on gene homology and high-resolution zoo-FISH. Genomics 74, 287-298
Pataer A, Kamoto T, Lu LM, Yamada Y, Hiai H (1996) Two dominant host resistance genes to pre-B lymphoma in wild-derived inbred mouse strain MSM/Ms. Cancer Res 56, 3716-3720
Pharoah PDP, Antoniou A, Bobrow M, Zimmern RL, Easton DE, et al. (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31, 33-36
Rapp JP (2000) Genetic analysis of inherited hypertension in the rat. Physiol Rev 80, 135-172
Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, et al. (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69, 138-147
Roshani L, Mallon P, Sjostrand E, Wedekind D, Szpirer J, et al. (2005) Genetic analysis of susceptibility to endometrial adenocarcinoma in the BDII rat model. Cancer Genet Cytogenet 158, 137-141
Russo IH, Russo J (1996a) Mammary gland neoplasia in long-term rodent studies. Environ Health Perspect 104, 938-967
Russo J, Russo IH (1996b) Experimentally induced mammary tumors in rats. Breast Cancer Res Treat 39, 7-20
Russo J, Russo IH (2000) Atlas and histologic classification of tumors of the rat mammary gland. J. Mammary Gland Biol Neoplasia 5, 187-200
Samuelson DJ, Haag JD, Lan H, Monson DM, Shultz MA, et al. (2003) Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats. Carcinogenesis 24, 1455-1460
Samuelson DJ, Aperavich BA, Haag JD, Gould MN (2005) Fine mapping reveals multiple loci and a possible epistatic interaction within the mammary carcinoma susceptibility quantitative trait locus Mcs5. Cancer Res 65, 9637-9642
SAS Institute Inc. (1991) SAS System for Linear Models, 3rd edn. (Cary, NC: SAS Institute Inc.)
Seaton G, Haley CS, Knott SA, Kearsey M, Visscher P (2002) QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinformatics 18, 339-340
Shepel LA, Gould MN (1999) The genetic components of susceptibility to breast cancer in the rat. Prog Exp Tumor Res 3, 158-169
Shepel LA, Lan H, Haag JD, Brasic GM, Gheen ME, et al. (1998) Genetic identification of multiple loci that control breast cancer susceptibility in the rat. Genetics 149, 289-299
Shull JD, Spady TJ, Snyder MC, Johanssson SL, Pennington KL (1997) Ovary-intact, but not ovariectomized female ACI rats treated with 17beta-estradiol rapidly develop mammary carcinoma. Carcinogenesis 18, 1595-1601
Szpirer C, Tissir F, Rivière M, Levan G, Szpirer J (1994) Assignment of the rat Jun family genes to Chromosome 19 (Junb), Chromosome 5q31-33 (Jun), and Chromosome 16 (Jund). Mamm Genome 5, 361-364
Tanuma J, Shisa H, Hiai H, Higashi S, Yamada Y, et al. (1998) Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat. Cancer Res 58, 1660-1664
Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, et al. (1996) The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 12, 333-337
The CHEK2-Breast Cancer Consortium(2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31, 55-59
Ushijima T, Yamamoto M, Suzui M, Kuramoto T, Yoshida Y, et al. (2000) Chromosomal mapping of genes controlling development, histological grade, depth of invasion, and size of rat stomach carcinomas. Cancer Res 60, 1092-1096
Visscher PM, Thompson R, Haley CS (1996) Confidence intervals in QTL mapping by bootstrapping. Genetics 143, 1013-1020
Watanabe TK, Bihoreau MT, McCarthy LC, Kiguwa SL, Hishigaki H, et al. (1999) A radiation hybrid map of the rat genome containing 5,255 markers. Nat Genet 22, 27-36
Wendell DL, Gorski J (1997) Quantitative trait loci for estrogen-dependent pituitary tumor growth in the rat. Mamm Genome 8, 823-829
Wooster R, Bignell G, Lancaster J, Swift S, Seal S, et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789-792
Yamada Y, Matsushiro H, Ogawa MS, Okamoto K, Nakakuki Y, et al. (1994) Genetic predisposition to pre-B lymphomas in SL/Kh strain mice. Cancer Res 54, 403-407
Zhang R, Haag JD, Gould MN (1990) Site of expression and biological function of the rat mammary carcinoma suppressor gene. Carcinogenesis 11, 1765-1770
