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Separation of high mammary tumor incidence from high hepatoma incidence in backcross mice during segregation of the viable yellow gene
Author(s) -
Smith Gilbert H.,
Vlahakis George
Publication year - 1982
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910290516
Subject(s) - mouse mammary tumor virus , biology , provirus , backcrossing , mammary tumor , mammary gland , endogeny , carcinogenesis , gene , microbiology and biotechnology , genetics , endocrinology , medicine , cancer , breast cancer , genome
Mammary tumorigenesis in strain C3H‐ vy fB female mice (approximately 90% incidence) is not due to exogenous mouse mammary tumor virus (MMTV) but to genetic factors transmitted by either parent. Prominent among these genetic factors is the viable yellow (A vy ) gene which may increase either the virulence of the endogenous MMTV provirus (Mtv‐l) by promoting expression or the susceptibility of the mammary tissue to tumorigenesis by endogenous MMTV. Crosses were made between the viable yellow strain, C3H‐A vy fB/He(A vy A ay ) and C3H/Sm (AA) to give heterozygous (A vy A) F 1 yellow hybrids from which yellow (A vy ) and agouti (AA) back‐cross progeny were produced by mating with C3H/Sm males. A vy A backcross females were expected to have at least twice as many mammary tumors as the AA back‐cross females if the A vy gene were solely responsible for the high incidence of mammary tumors in C3H‐A vy fB since mammary tumor incidence is 90% in A vy fB and 40% in (AA)C3HfB. Alternatively, if the high tumor incidence in C3H‐A vy B were due to a more active endogenous MMTV (Mtv‐l), then a much smaller difference in the mammary tumor incidence of A vy A versus AA backcross females would be expected. The more reactive endogenous MMTV would occur equally between yellow and agouti females, since the C3H Mtv‐l gene is present on a separate chromosome from the A vy gene. Unexpectedly, the F 1 hybrid females (A vy A) developed mammary tumors at a relatively low rate (28.9%) although hepatoma incidence remained high (89.5%). Both yellow (A vy A) and agouti (AA) backcross females showed an even greater reduction in mammary tumor incidence, 7.9% and 3.8% respectively. In contrast, the high rate of spontaneous hepatoma development segregated with the A vy gene since 86‐5% of the yellow (A vy A) backcross females development hepatomas by 19 months of age, while only 25% of the agouti (AA) backcross females had liver tumors at 24.4 months. The reduction of mammary tumor incidence in (C3H‐A vy fB × C3H/Sm)F 1 hybrids was unexpected since earlier studies had shown that reciprocal F 1 , hybrids between strains BALB/c and C3H‐A vy fB continued to show a 90% mammary tumor incidence. The present result is consistent with the possibility that strain C3H/Sm possesses a heritable factor(s) which attenuates the ability of endogenous MMTV to malignantly transform mammary epithelium.