Protein tyrosine phosphatase epsilon increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Accurate phosphorylation of tyrosine residues in proteins plays a central r ole in regulation of cellular function. Although connections between aberra nt tyrosine kinase activity and malignancy are well-established, significan tly less Is known about the roles of protein tyrosine phosphatases (PTPases ) in tumorigenesis. We have previously shown that the transmembranal form o f PTPase Epsilon (PTP epsilon) is upregulated in mouse mammary tumors initi ated specifically by ras or neu, suggesting that PTP epsilon may play a rol e in transformation by these two oncogenes, In order to test this notion li t vivo, we created transgenic mice that express elevated le, els of PTP eps ilon in their mammary epithelium by use of the MMTV promoter/enhancer, Foll owing several cycles of pregnancy female MMTV-PTP epsilon mice uniformly de , eloped pronounced and persistent mammary hyperplasia which was accompanie d by residual milk production. Solitary mammary tumors were often detected secondary to mammary hyperplasia. The sporadic nature of the tumors, the lo ng latency period prior to their development, and low levels of transgene e xpression in the tumors indicate that PTP epsilon provides a necessary, but insufficient, signal for oncogenesis. The results provide genetic evidence that PTP epsilon plays an accessory role in production of mammary tumors i n a manner consistent with its upregulation in mammary tumors induced by ra s or neu.