Abnormal Mammary Development in STAT1-null Mice is Stroma-Dependent

ABSTRACT: Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor-positive mammary tumors with incomplete penetrance and long latency. We studied the growth and development of the mammary glands in Stat1-null mice. Stat1-null MGs have faulty branching morphogenesis with abnormal terminal end buds. The Stat1-null MG also fails to sustain growth of 129S6/SvEv wild-type and null epithelium. These abnormalities are partially reversed by added progesterone and prolactin. Transplantation of wild-type bone-marrow into Stat1-null mice does not reverse the mammary gland developmental defects. Media conditioned by Stat1-null epithelium-cleared mammary fat pads does not stimulate epithelial proliferation whereas it is stimulated by conditioned media derived from either wild-type or progesterone and prolactin-treated Stat1-null epithelium-cleared mammary fat pads. Microarrays and multiplex cytokine protein assays showed that the mammary gland of Stat1-null mice had lower levels of growth factors that have been implicated in normal mammary gland growth and development. Transplanted Stat1-null tumors and their isolated cells also grow slower in Stat1-null mammary gland compared to wild-type recipient mammary gland. Stat1-null hosts responded to tumor transplants with granulocytic infiltrates while wild-type hosts show a mononuclear response. These studies demonstrate that growth of normal and neoplastic Stat1-null epithelium primarily depends on the hormonal milieu and factors, such as cytokines, from the mammary stroma. Stat1-null mammary glands were compared to 129SvEv WT mammary glands with respect to development, gene expression profiles, growth factors and histology.

ORGANISM(S): Mus musculus

SUBMITTER: Clifford Tepper 

PROVIDER: E-GEOD-63025 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress