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1 March 2012 Research Article: A comparison of the E-cadherin-regulated Ras-MAP kinase pathways in two breast cancer cell lines
Daniel J. Kelpsch, Lauren E. Williams, Amy Du, Christopher L. Hulstein, Michael F. Lahey, Meera K. Advani, Stacey L. Raimondi
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Abstract

Breast cancer is the second leading cause of cancer death in women, with 1 in 8 developing an invasive breast cancer in her lifetime. Changes in gene expression are common as tumors progress and epigenetics studies alterations in gene expression where the coding DNA sequence is not directly changed. One epigenetic method employs DNA methylation in which DNA methyltransferases (DNMTs) can methylate, or silence, genes. A variety of cancer cell lines have been shown to express aberrantly spliced DNMTs. Furthermore, the aberrant transcripts DNMT3B7 and ΔDNMT3B6 have been shown to be highly expressed in invasive breast cancers compared to poorly invasive cells. Interestingly, DNMT3B7 was shown to methylate the E-cadherin gene, CDH1. The loss of E-cadherin expression and p120 isoform alterations is a hallmark of tumor progression to a more invasive state. Recently, it has been shown that loss of E-cadherin expression can activate the Ras/MAPK pathway via p120 and Rac signaling in breast cancer cells. Based on these data, we hypothesize that the expression of DNMT3B7 and ΔDNMT3B6 in breast cancer cells decreases E-cadherin expression, thus promoting tumor progression through over-activation of the Ras/MAPK pathway via p120. This study gives clear evidence of expression changes in E-cadherin and p120 isoforms leading to the activation of Rac and the Ras/MAPK pathway in the highly invasive MDA-MB-231 breast cancer cell line as compared to the poorly invasive MCF-7 breast cancer cells. Future studies on this topic may lead to the development of novel therapeutics in the treatment of breast cancer.

Daniel J. Kelpsch, Lauren E. Williams, Amy Du, Christopher L. Hulstein, Michael F. Lahey, Meera K. Advani, and Stacey L. Raimondi "Research Article: A comparison of the E-cadherin-regulated Ras-MAP kinase pathways in two breast cancer cell lines," BIOS 83(1), 17-25, (1 March 2012). https://doi.org/10.1893/0005-3155-83.1.17
Received: 9 April 2011; Accepted: 1 July 2011; Published: 1 March 2012
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