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

Mammary TGFα overexpression results in delayed involution and eventually mammary cancer in transgenic mice. We hypothesized that STATs and PRL receptors (PRLR), critical regulators of mammary function, are altered in these 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-lactation) in WAP-TGFα transgenic mice and non-transgenic controls. Long form PRLR mRNA in WAP-TGFα glands at both pregnant d.18 and d.4 post-lactation was significantly reduced compared to controls, and PRLR-S3 failed 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-TGFα glands. STAT 5a and 5b were lower at late pregnancy, but higher post-lactation; however, pTyr⁶⁹⁴ STAT 5 was abnormally low at both times. Thus overexpression of TGFα has direct or indirect effects on both STATs and PRL responsiveness in vivo, which may reflect mechanisms of TGFα-induced mammary epithelial abnormalities.