BP1, A HOMEOBOX GENE, IS OVER EXPRESSED IN BREAST CANCER

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We have cloned a potential new human oncogene called BP1 which belongs to an important family of genes referred to as homeobox genes. BP1 was originally identified as a repressor of the human beta globin gene; recent studies in our laboratory demonstrated that BP1 mRNA if over-expressed in 81% of pediatric and 47% of adult acute myeloid leukemias, possibly in early progenitors. In addition, over-expression was observed in 32% of pediatric T-cell acute lymphoblastic leukemia (ALL), although not in pediatric pre-B-ALL. Our molecular studies showed that over-expression of BP1 leads to increased growth and decreased erythroid differentiation in cell lines, indicating a possible mechanism by which BP1 could function as an oncogene. We now have preliminary data implicating BP1 expression in breast cancer. Analysis of seven breast cancer cell lines showed BP1 mRNA levels ranging from barely detectable to highly expressed. Interestingly, cell lines highly expressing BP1 are tumorigenic. BP1 mRNA was highly expressed in 87% of fifteen breast cancer tumors we have examined while, in contrast, it was expressed at a very low level in one of five normal breast tissue. BP1 expression was seen in 100% of the high grade, estrogen receptor (ER) negative and progesterone receptor (PR) negative cancers but in only 33% of ER positive, PR positive breast cancers. In this proposal we will test the hypothesis that BP1 is a new molecular marker in breast cancer by analyzing its expression in a larger cohort of breast tumors and determining whether a correlation exists between its expression and clinical prognosis. Clinical data is available which will allow us to determine correlations between BP1 expression and node status or tumor grade. Analysis of four specimens to determine whether there is an association between BP1 expression and aberrant expression of any of these genes. This multi-parameter study will therefore determine the clinical relevance of BP1 expression breast cancer.