title: Genetic identification of distinct loci controlling mammary tumor multiplicity, latency, and aggressiveness in the rat.
abstract: 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.
authors.affiliation: Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Rue Profs Jeener & Brachet, 12, Gosselies, B-6041, Belgium.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Quan
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Laes
authors.forename: Daniel
authors.initials: D
authors.lastname: Stieber
authors.forename: Michèle
authors.initials: M
authors.lastname: Rivière
authors.forename: Jose
authors.initials: J
authors.lastname: Russo
authors.forename: Dirk
authors.initials: D
authors.lastname: Wedekind
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.forename: Frédéric
authors.initials: F
authors.lastname: Farnir
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Josiane
authors.initials: J
authors.lastname: Szpirer
authors.forename: Claude
authors.initials: C
authors.lastname: Szpirer
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene