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

我们已经克隆了一个潜在的新的人类癌基因BP1，它属于一个重要的基因家族，被称为同源异型盒基因。BP1最初被鉴定为人类β珠蛋白基因的阻遏物;我们实验室最近的研究表明，BP1 mRNA在81%的儿童和47%的成人急性髓性白血病中过度表达，可能在早期祖细胞中。此外，在32%的儿童T细胞急性淋巴细胞白血病（ALL）中观察到过度表达，尽管在儿童前B-ALL中没有观察到。我们的分子研究表明，BP1的过度表达导致细胞系中生长增加和红系分化减少，这表明BP1可以作为癌基因发挥作用的可能机制。我们现在有初步的数据表明BP1在乳腺癌中的表达。对7个乳腺癌细胞系的分析显示，BP1 mRNA水平从几乎检测不到到高度表达。有趣的是，高度表达BP1的细胞系是致瘤的。BP1 mRNA在我们检测的15个乳腺癌肿瘤中的87%中高度表达，而相比之下，它在5个正常乳腺组织中的一个中以非常低的水平表达。BP1表达见于100%的高级别、雌激素受体（ER）阴性和孕激素受体（PR）阴性乳腺癌，但仅见于33%的ER阳性、PR阳性乳腺癌。在本研究中，我们将通过分析BP1在一个较大的乳腺肿瘤队列中的表达，并确定其表达与乳腺癌临床分期之间是否存在相关性，来检验BP1是乳腺癌新分子标志物的假设。 预后临床数据是可用的，这将使我们能够确定BP1表达与淋巴结状态或肿瘤分级之间的相关性。分析四个标本，以确定是否有BP1的表达和这些基因的任何异常表达之间的关联。因此，该多参数研究将确定BP1表达乳腺癌的临床相关性。

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.