In the present study, we found that EGFR was located on the cell surface of mammary LY333531 purchase gland epithelial cells in five-month-old TA2 mice, while no nuclear EGFR was detected.
In contrast, nuclear EGFR was detected in epithelial cells from normal mammary glands removed from spontaneous breast cancer-bearing TA2 mice as well as in breast cancer cells from those animals. In order to confirm the function of nuclear EGFR, we detected the expression of cyclin D1. A positive correlation between nuclear EGFR and cyclin D1 expression was observed both in mammary gland samples and breast cancer samples of cancer-bearing TA2 mice. The same result has also been observed in a cohort of breast carcinoma patients. Our results suggest that nuclear translocation of EGFR may occur with increasing age, and that nuclear EGFR can promote the expression of cyclin D1, leading to a high proliferation index
in mammary epithelial cells. Proliferating cell nuclear antigen (PCNA), the maestro of the replication Selleck RXDX-101 fork, is a cofactor of DNA polymerases [26, 27]. PCNA is now one of the most commonly used molecules to detect the proliferation index of tumor cells. Our results indicated that the mammary epithelial cells from cancer-bearing TA2 mice had a higher proliferation index (PCNA labeling index) than those of the five-month-old TA2 mice, and this was further confirmed by real-time PCR. In order to know whether nuclear EGFR could affect the expression of PCNA we also detected PCNA by immunohistochemical staining and real-time PCR. No correlation was found between PCNA and EGFR expression. Our results confirm that nuclear EGFR can indirectly up-regulate the expression of cyclin D1. Farnesyltransferase In the present study, expression profiles data showed that EGFR expression was down-regulated in cancer tissues compared with that of the matched mammary glands, in contrast to results previously reported for human breast cancer. In order to confirm our findings, we detected EGFR expression by real-time PCR and immunohistochemical staining.
The results of real-time PCR and immunohistochemical staining were consistent with those of the gene arrays. As we know, EGFR is one of the prognostic factors and therapeutic targets for human breast cancers. According to our results, EGFR may have different effect on the progression of breast cancer of TA2 mice and human beings. For TA2 mice, high level of EGFR played an important role in the carcinogenesis of its mammary gland epithelial cells, which needs further exploration. Conclusions In briefly, our data suggest that the expression of decorin, EGFR and cyclin D1 in mammary epithelial cells changes with increasing age. Anestric mammary epithelial cells from five-month-old mice expressed low levels of EGFR. The kinase activity of this EGFR may have been attenuated in part by decorin.