Dysregulation of mammary Stats 1, 3 and 5 and PRL receptors by overexpression of TGF alpha

Mammary TGF alpha overexpression results in delayed involution and eventual ly mammary cancer in transgenic mice. We hypothesized that STATs and PRL re ceptors (PRLR), critical regulators of mammary function, are altered in the se animals and may contribute to this phenotype. We examined these factors late in the first pregnancy (d.18) and during normal involution (d.4 post-l actation) in WAP-TGF alpha transgenic mice and non-transgenic controls. Lon g form PRLR mRNA in WAP-TGF alpha glands at both pregnant d.18 and d.4 post -lactation was significantly reduced compared to controls, and PRLR-S3 fail ed to rise during involution. Total and pTyr STAT 1, 3, 5a and 5b also were altered. STAT 3 was higher at both times in WAP-TGF alpha glands. STAT 5a and 5b were lower at late pregnancy, but higher post-lactation; however, pT yr(694) STAT 5 was abnormally low at both times. Thus overexpression of TGF alpha has direct or indirect effects on both STATs and PRL responsiveness in vivo, which may reflect mechanisms of TGF alpha -induced mammary epithel ial abnormalities. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.