Opposite effects of modifiers of the ApcMin mutation in intestine and mammary gland.
Patterns of tumor susceptibility in different organs are widely divergent in mouse strains: one strain may be highly susceptible to tumors in one organ but resistant in another organ, whereas another strain may exhibit the opposite pattern (P. Demant, Semin. Cancer Biol., 3: 159-166, 1992). Therefore, susceptibility to tumors in different organs is assumed to be controlled by different sets of genes. On the other hand, many oncogenes and tumor suppressor genes are mutated in tumors from different organs, indicating that similar tumorigenic pathways operate in various tissues. To obtain insight into the interactions of susceptibility genes with one of such pathways, we compared tumorigenesis in intestine and mammary gland in recombinant congenic strains (RCSs) carrying the Apc(Min) mutation, affecting the Wnt pathway. The presence of Apc(Min) increased considerably the incidence of intestinal and mammary tumors. The individual RCSs differed in the number and latency of Apc(Min)-induced intestinal and mammary tumors and histological type of the latter. Unexpectedly, the strain distribution of susceptibility to the intestinal and mammary tumors in the Apc(Min)-bearing mice was opposite in the RCSs; the strains most susceptible for intestinal tumors were most resistant to mammary tumors and vice versa. This suggests that a set of genes controls the impact of the Apc(Min) mutation in both organs but with opposite effects. Elucidation of the basis of the observed strain differences in organ-specific Wnt pathway-mediated tumorigenesis will help to understand the interactions between germ-line encoded allelic differences in susceptibility genes and the spectrum of somatic mutations in tumor cells.
Czarnomska
Alina
A
Department of Genetics and Laboratory Animal Breeding, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Krysiak
Elzbieta
E
Piskorowska
Joanna
J
Sitarz
Miroslawa
M
Pysniak
Kazimiera
K
Pilcík
Tomás
T
Demant
Peter
P
D000818:Animals; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D007414:Intestinal Neoplasms / Q000235:genetics*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation