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Expression of two novel eph-related receptor protein tyrosine kinases in mammary gland development and carcinogenesis
A C Andres1, H H Reid, G Zürcher
1Laboratory for Clinical and Experimental Research, University of Bern, Switzerland.
Abstract:
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.
Insights
Two protein tyrosine kinases (PTKs), myk-1 and myk-2, are involved in mammary gland growth. Their expression increases with proliferation and decreases with differentiation, particularly in invasive tumors.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Protein tyrosine kinases (PTKs) play crucial roles in cellular growth and differentiation.
- Understanding PTK involvement in mammary epithelial cell growth is essential for cancer research.
Purpose of the Study:
- To identify PTKs involved in mammary epithelial cell growth control.
- To investigate the expression patterns of identified PTKs during mammary gland development and tumorigenesis.
Main Methods:
- PCR-based cloning to identify PTKs in mouse mammary epithelial cells.
- Northern blot analysis to examine gene expression in mammary glands at various developmental stages.
- Analysis of PTK expression in transgenic mouse models of mammary tumors (Ha-ras and c-myc).
Main Results:
- Identified two novel eph-related receptor PTKs, myk-1 and myk-2.
- myk-1 and myk-2 expression is induced at puberty and regulated during the estrus cycle.
- Expression is down-regulated during pregnancy-induced differentiation and over-expressed in undifferentiated, invasive mammary tumors (Ha-ras model), but not in well-differentiated tumors (c-myc model).
Conclusions:
- myk-1 and myk-2 are implicated in mammary gland proliferation.
- Their expression is inversely correlated with mammary gland differentiation.
- These PTKs may serve as markers for mammary tumor invasiveness.