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

BP1 是一种同源盒基因，在乳腺癌中过度表达

• 批准号: 6287632
• 负责人: Patricia E Berg
• 金额: $ 7.6万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6287632
• 关键词: breast neoplasms; cyclins; epidermal growth factor; female; gene expression; genetic markers; growth factor receptors; homeobox genes; human tissue; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; outcomes research; p53 gene /protein; prognosis; protooncogene

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.

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，被称为同源框基因。BP1最初被认为是人类β珠蛋白基因的抑制子；最近我们实验室的研究表明，BP1 mRNA在81%的儿童和47%的成人急性髓系白血病中过度表达，可能在早期祖细胞中。此外，32%的儿童T细胞急性淋巴细胞白血病(ALL)有过度表达，而在儿童Pre-B-ALL中则没有。我们的分子研究表明，BP1的过度表达导致细胞系生长增加和红系分化减少，表明BP1可能是一种癌基因发挥作用的机制。我们现在有初步数据表明BP1在乳腺癌中的表达。对7个乳腺癌细胞株的分析显示，BP1的mRNA水平从几乎检测不到到高表达。有趣的是，高表达BP1的细胞系具有致瘤性。BP1mRNA在我们检查过的15个乳腺癌肿瘤中有87%高表达，而相比之下，在5个正常乳腺组织中只有一个表达水平很低。在雌激素受体(ER)阴性、孕激素受体(PR)阴性的高级别乳腺癌中，BP1的阳性表达率为100%，而在ER阳性、PR阳性的乳腺癌中BP1的阳性表达率仅为33%。在这项建议中，我们将通过分析BP1在更大的乳腺肿瘤队列中的表达，并确定其表达与临床预后之间是否存在相关性，来检验BP1是乳腺癌新的分子标志物的假设。临床数据将使我们能够确定BP1表达与结节状态或肿瘤分级之间的相关性。对四个样本进行分析，以确定BP1的表达与这些基因中任何一个的异常表达之间是否存在关联。因此，这项多参数研究将确定BP1表达与乳腺癌的临床相关性。