Ovarian hyperstimulation by LH leads to mammary gland hyperplasia and cancer predisposition in transgenic mice.
Many risk factors for breast cancer are associated with hormonally regulated events. Although numerous mouse models of mammary cancer exist, few address the roles of hormones in spontaneous tumor formation. Here we report that transgenic mice that overexpress LH, resulting in ovarian hyperstimulation, undergo precocious mammary gland development. A significant increase in proliferation leads to ovary-dependent mammary gland hyperplasia. Transgenic glands morphologically mimic those of wild-type pregnant mice and expression levels of multiple milk protein genes are comparable with what is observed at d 14 of pregnancy. In addition to sustained hyperplasia, spontaneous mammary tumors were observed with a mean latency of 41 wk, indicating that chronic hormonal stimulation causes mammary cancer. Although hormonally induced, these tumors lack expression of progesterone receptor, suggesting that following initiating events, the tumors may become hormone independent. This mouse model likely holds great potential as a tool for discovery of hormone-mediated mechanisms of breast cancer and identification of future targets for breast cancer prevention and treatment.
Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA.
Erin L
EL
Milliken
Rebecca K
RK
Ameduri
Melissa D
MD
Landis
Alireza
A
Behrooz
Fadi W
FW
Abdul-Karim
Ruth A
RA
Keri
D000818:Animals; D005260:Female; D015870:Gene Expression; D006965:Hyperplasia; D007986:Luteinizing Hormone / Q000235:genetics* / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000737:chemistry / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology; D010641:Phenotype; D011247:Pregnancy; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors
D008894:Milk Proteins; D011980:Receptors, Progesterone; D007986:Luteinizing Hormone