Abstract
The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal transduction pathways. Aberrant expression of specific receptor tyrosine kinases (RTKs) has been implicated in the genesis of a significant proportion of sporadic human breast cancers. Indeed, mammary epithelial expression of activated RTKs such as ErbB2/neu in transgenic mice has resulted in the efficient induction of metastatic mammary tumours. Although it is clear from these studies that activation these growth factor receptor signalling cascades are directly involved in mammary tumour progression, the precise interaction of each of these signalling pathways in mammary tumourigenesis and metastasis remains to be elucidated. The present review focuses on the role of several specific signalling pathways that have been implicated as important components in RTK-mediated signal transduction. In particular, it focuses on two well characterized transgenic breast cancer models that carry the polyomavirus middle T(PyV mT) and neu oncogenes.
Highlights
The ability of mammary epithelial cells to respond to growth factor is dependent on specific growth factor receptors that are coupled to a number of intracellular signalling pathways
The development of the mammary gland is thought to involve a series of defined steps that consist of cell proliferation, differentiation and programmed cell death
After the pups have been weaned from the lactating mother, the mammary epithelium undergoes a rapid involution through the induction of programmed cell death
Summary
The ability of mammary epithelial cells to respond to growth factor is dependent on specific growth factor receptors that are coupled to a number of intracellular signalling pathways. The primary mechanism by which ErbB2 induces mammary tumourigenesis in human breast cancer is through overexpression of the wild-type receptor Another potent tyrosine kinase that is implicated in murine mammary tumourigenesis and metastasis is that associated with PyV mT antigen [16]. Like PyV mT transformed tumour cells, http://breast-cancer-research.com/content/2/3/211 c-Src derived from the Neu-induced mammary tumour cells is complexed with a 89-kDa phosphotyrosine protein that appears to be specific to the mammary epithelium [24]. Mammary-specific expression of a mutant PyV mT oncogene decoupled from the Shc/Grb[2] signalling molecules results in the induction of widespread mammary epithelial hyperplasias [15]. Future studies to investigate the role of Neu-coupled signalling molecules in mammary tumour progression should provide important insight into the molecular basis of breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
