Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist.
Several reports have provided evidence that body size early in life is positively correlated with risk of subsequent breast cancer, but the biological basis for this relationship is unclear. We examined tumour incidence in transgenic mice expressing a growth hormone (GH) antagonist and in non-transgenic littermates following exposure to dimethylbenz[ a ]anthracene (DMBA), a well characterized murine mammary gland carcinogen. The transgenic animals had lower IGF-I levels, were smaller in terms of body size and weight, and exhibited decreased tumour incidence relative to controls. The demonstration that both body size early in life and breast cancer incidence are influenced by experimental perturbation of the GH-IGF-I axis in a transgenic model provides evidence that variability between individuals with respect to these hormones underlies the relationship between body size early in life and breast cancer risk observed in epidemiological studies.
Pollak
M
M
Cancer Prevention Research Unit of the Jewish General Hospital and McGill University, Montreal, Quebec, H3T 1E2, Canada.
Blouin
M J
MJ
Zhang
J C
JC
Kopchick
J J
JJ
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001724:Birth Weight; D002273:Carcinogens / Q000633:toxicity; D018450:Disease Progression; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone