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Oncogene

Title:		Prolactin gene-disruption arrests mammary gland development and retards T-antigen-induced tumor growth
Author(s):		Vomachka AJ; Pratt SL; Lockefeer JA; Horseman ND;
Address:		"Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, OH 45267-0576, USA"
Journal Title:		Oncogene
Year:		2000
Volume:		19
Issue:		8
Page Number:		1077 - 1084
DOI:		10.1038/sj.onc.1203348
ISSN/ISBN:		0950-9232 (Print) 0950-9232 (Linking)
Abstract:		"Prolactin (PRL), interacting with other hormones from the pituitary, gonad, and placenta, activates specific signals that drive the appropriately timed morphological and functional development of the mammary gland. A mouse model of isolated PRL deficiency (PRL-/-) was created by gene disruption in an effort to further understand the molecular basis of mammary gland development and breast cancer. Whereas primary ductal growth was normal in PRL-/- mice, ductal arborization was minimal (branches/mm2=1.5+/-0.5), and lobular budding was absent. Replacement therapy with PRL injections stimulated a modest degree of lobular budding and ductal arborization (3.75+/-0.9). Pituitary transplants to the kidney capsule of PRL-/- mice restored lobular budding and ductal arborization, to the full extent of that seen in control animals (20. 3+/-5.5). Pregnancy, established by mating progesterone-treated PRL-/- females with PRL-/- males, led to complete morphological development of the mammary gland, appropriate to the gestational stage. PRL treatment stimulated tyrosine phosphorylation and DNA binding activity of Stat5a, but not Stat1 in PRL-/- or PRL+/- females, and Stat5a, but not Stat1, was elevated by estradiol within 24 h. PRL-deficient mice were crossed with mice expressing a dominant oncogene (polyoma middle-T antigen driven by the MMTV promoter, PyVT mice). Palpable (1 mm3) tumors were detected an average of 9 days earlier in hormonally normal females (PRL+/-:PyVT) compared with littermates that were PRL-deficient (PRL-/-:PyVT). The growth rate of PyVT-induced tumors was 30% faster in PRL+/-, than in PRL-/- females"
Keywords:		"Adenocarcinoma/genetics/pathology Animals Antigens, Polyomavirus Transforming/*genetics DNA-Binding Proteins/drug effects/metabolism Female Mammary Glands, Animal/drug effects/*growth & development/metabolism Mammary Neoplasms, Experimental/*genetics/*pat;"
Notes:		"MedlineVomachka, A J Pratt, S L Lockefeer, J A Horseman, N D eng Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 2000/03/14 Oncogene. 2000 Feb 21; 19(8):1077-84. doi: 10.1038/sj.onc.1203348"