Expression of transcription factor BP1 is an early event in the immortalization continuum to breast cancer

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The MCF-10 series of cell lines represents many steps in breast cancer initiation, development, and progression. MCF-10F and MCF-10A cells are spontaneously immortalized human breast epithelial cells derived from a sample of fibrocystic disease. The transcription factor BP1, a member of the DLX homeobox gene family has been shown to have an oncogenic role in breast cancer. BP1 mRNA levels were analyzed in MCF-10 cell lines using real time PCR in a series that included initial untransformed outgrowths (MCF-10F and MCF-10A) and 6 transformed cell lines recapitulating various stages of benign proliferation (MCF10-AT1, MCF-10AT1kcl2), carcinoma in situ (MCF-10CA1h cl13), and invasive carcinoma (MCF-10CA1d cl1, MCF-10CA1a cl1 p44 and p80). BP1 expression was measured as a ratio of BP1 to B-actin (housekeeping reference control). RNA from normal individuals did not express BP1. Levels of BP1 (two times the B-actin level) in immortalized MCF-10F and MCF-10A were progressively higher (2.5 times B-actin expression levels) in the subsequent transformed precursor progeny MCF-10AT1 and MCF-10AT1Kcl2 with a significant reduction of BP1 expression in subsequent progeny that recapitulated DCIS (MCF-10CA1h cl13) and carcinoma (MCF-10CA1d cl1, MCF-10CA1a cl1 p44 and p80). These data indicate that abnormal BP1 expression is a very early target in the immortalization continuum with increased levels in transformation, and with tapering but persistent BP1 expression through progression events leading to breast malignancy. Supported by National Institutes of Health NIH CA 70923, DAMD DAMD17-00-1-0288 and DAMD17-02-1-0406