Expression of two novel eph-related receptor protein tyrosine kinases in mammary gland development and carcinogenesis.

To investigate the involvement of protein tyrosine kinases (PTKs) in the growth control of mammary epithelial cells, we have used PCR based cloning to identify PTKs expressed in a mouse mammary epithelial cell line. This approach led to the isolation of two receptor PTKs of the eph-related subfamily; myk-1, a novel member expressed predominantly in lung, heart and mammary gland and myk-2, a close relative of the human eck gene. Northern blot analysis of RNA from mouse mammary glands at different stages of development revealed that myk-1 and myk-2 expression is induced at puberty and differentially regulated during the estrus cycle. myk-1 and myk-2 expression was down-regulated during the pregnancy induced differentiation of the mammary gland. Over-expression of myk-1 and myk-2 was found in the undifferentiated and invasive mammary tumors of transgenic mice expressing the Ha-ras oncogene. In contrast, no elevated expression of either gene could be detected in the well differentiated and non-metastatic mammary tumors of c-myc expressing transgenic mice. These results indicate that myk-1 and myk-2 expression is induced during the proliferation of the mammary gland and down-regulated by its differentiation.