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Role of the AREB6/ZEB Transcription Factor in Invasive Breast Cancer

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Annual summary 19 Apr 2002-18 Apr 2004

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The major goal of this study was to investigate whether the estrogen-inducible transcription factor ZEB-1 contributed to the progression of breast carcinoma. For this study, we pursued and obtained sufficient numbers of staged, matched breast cancer biopsy tissues. I developed a novel protocol for multiplex real-time PCR so we could analyze the expression of four genes in one reaction simultaneously. The second year of work on these projects showed great progress and completion of our goals. Keeping in mind a new family member, ZEB-2, I designed and performed the real-time assays on a number of breast tissue samples. We found that the expression of both ZEB-1 and ZEB-2 are significantly increased in invasive breast cancers, compared to their normal match tissue, and ZEB-1 is no longer under the regulation of estrogen. To investigate the possibility of gene amplification, I created a ZEB-1 specific DNA program for quantitative Southern blot analysis and have successfully tested this probe on ovarian tissue biopsies. I have also constructed the ecdysone-inducible MCF-7 cell line that is needed for Task 4. In this line, ZEB-1 expression can be turned on or off with the presence or absence of ecdysone, and thus the ability of ZEB-1 to promote cell invasion can now be studied by Matrigel invasion assay. In support of our hypotheses, we have shown that ZEB-1 expression correlates with invasive breast cancer and that its expression is no longer regulated by estrogen.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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