To test this hypothesis,

we used tissue samples taken from TA2 mice. Gene expression arrays revealed that several imprinted genes, oncogenes and tumor suppressor genes were differentially expressed between normal mammary glands and spontaneous breast cancer tissues. Some of these genes encoded Mocetinostat stromal constituents such as versican and decorin. Decorin is synthesized by the majority of mesenchymal cells [18]. However, it also interacts with a variety of other ECM components and can affect cell growth. It has been shown that decorin functionally inactivates the ErbB2 protein in breast carcinoma cells [18], leading to growth suppression and cytodifferentiation of mammary carcinoma cells. Reduced expression of decorin may facilitate cell growth, tumorigenesis and metastasis[9, 19]. In human breast cancer tissues, decorin levels were decreased 2-5-fold when compared to BMS202 supplier normal breast tissue[14]. Treatment with decorin protein reduced primary tumor growth by 70% and eliminated observable metastasis in an orthotopic mammary carcinoma animal model injected with a metastatic breast cancer cell line. Adenoviral overexpression of decorin caused primary tumor retardation of 70%, in addition to greatly reducing the observation of metastasis [20]. The expression arrays revealed that decorin was down-regulated in tumor tissues, so we speculate

that loss of decorin expression may contribute to the high proliferation of mammary epithelial cells. As a component of the ECM, Poziotinib price decorin can bind several growth factors and their receptors, such as EGFR. After binding EGFR, decorin can inhibit cell proliferation by up-regulating the expression of p21. EGFR on the cell surface is thought to play a pivotal role in cell proliferation, cell migration, and cell survival, but Marti et al.[21] also reported a nuclear distribution for EGFR, now called “”nuclear EGFR,”" in primary adrenocortical carcinomas more than a decade ago. High levels of nuclear EGFR have

subsequently been reported in many tumors, including those of the human breast, thyroid and cervix [22, 23]. Thus two different signaling pathways, cytoplasmic/traditional and nuclear, have been identified. The cytoplasmic EGFR pathway often leads selleck inhibitor to tumorigenesis, tumor proliferation, metastasis, chemoresistance and radioresistance through the activation of Ras, PI-3K and STATs. The nuclear EGFR signaling pathway can escape the traditional transduction cascades and has different functions that depend on down-stream signaling molecules. Nuclear EGFR interacts with the DNA-binding transcription factors E2F1 and STAT3, and can accelerate G1/S cell cycle progression by up-regulating the expression of cyclin D1 and B-Myb. Cyclin D1 is a well-known oncogene whose overexpression is found in many cancers and is related to tumor progression and metastasis. Consistent with this mechanism, nuclear accumulation of EGFR is also associated with increased cell proliferation [22].