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A Novel HOX Gene Target in Breast Cancer

乳腺癌中的新 HOX 基因靶标

基本信息

批准号：
6623512
负责人：
Patricia E Berg
金额：
$ 26.6万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-04-01 至 2005-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6623512
关键词：
antisense nucleic acid apoptosis breast neoplasms gene induction /repression homeobox genes human tissue immunocytochemistry neoplasm /cancer genetics neoplastic transformation polymerase chain reaction protein structure function transcription factor

项目摘要

DESCRIPTION (provided by applicant): Breast cancer is the leading cause of death among American women who are 35 to 55 years of age. We have cloned a novel human homeobox gene called BP1 which is a potential target for therapy of breast cancer. In tumors from 15 patients with newly diagnosed breast cancer, we found that 13 of the 15 (87%) expressed high levels of BP1 mRNA, whereas BP1 mRNA was undetectable in the remaining 13%. In contrast, BP1 was expressed (at a very low level) in only one of six normal breast tissues. BP1 expression was seen in 100% of the high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative cancers, but in only 33% of ER positive, PR positive breast cancers. Interestingly, BP1 mRNA levels were also found to be high in breast cancer cell lines which are known to be tumorigenic. In this application, we will test the hypothesis that BP1 is a new therapeutic target in breast cancer by analyzing additional tumors and using molecular techniques. Currently we are measuring BP1 in breast tumors by RT-PCR. In this application, immunohistochemical analysis will be developed to facilitate analysis of BP1 expression in histological sections. Of relevance to this grant, previous molecular studies in leukemia suggest that BP1 expression is transforming and is required for survival of a leukemia cell line. If BP1 is part of an anti-apoptotic pathway, its expression may be important in breast cancer cells as well. Stable breast cancer cell lines overexpressing BP1 will be established to determine whether BP1 expression is transforming in vitro. Analysis of a gene array using these cell lines will help to identify genes which may be targets of BP1 and pathways in which it is involved. To determine whether decreasing BP1 levels leads to growth inhibition or apoptosis, BP1 expression will be reduced in breast cancer cell lines using genetic and pharmacological methods. This study will therefore combine clinical and genetic approaches to determine the importance of BP1 expression in breast cancer.

描述（由申请人提供）：乳腺癌是美国35岁至45岁女性的主要死因。 55岁。我们克隆了一个新的人类同源异型盒基因BP 1，是乳腺癌治疗的潜在靶点。在15名患者的肿瘤中，在新诊断的乳腺癌中，我们发现15例中有13例（87%）表达了高水平的BP 1 mRNA，而BP 1 mRNA在其余组织中检测不到。百分之十三相比之下，BP 1在六个细胞中仅一个表达（以非常低的水平）。正常乳腺组织。BP 1在100%的高级别乳腺癌中表达，雌激素受体（ER）阴性、孕激素受体（PR）阴性癌症，而ER阳性、PR阳性乳腺癌仅占33%。有趣的是，BP 1 在乳腺癌细胞系中也发现mRNA水平很高，已知是致癌的。在本申请中，我们将检验以下假设： BP 1是乳腺癌的一个新的治疗靶点，肿瘤和使用分子技术。目前，我们正在测量BP 1，乳腺肿瘤的RT-PCR检测。在该应用中，免疫组织化学分析将有助于分析BP 1在组织学中的表达，路段与此相关的是，以前在白血病中的分子研究这表明BP 1的表达是转化性的，并且是一种细胞存活所必需的。白血病细胞系如果BP 1是抗凋亡途径的一部分，表达在乳腺癌细胞中也可能是重要的。稳定乳房将建立过表达BP 1的癌细胞系，以确定是否 BP 1表达在体外转化。使用这些分析基因阵列细胞系将有助于鉴定可能是BP 1靶点的基因，它所涉及的途径。为了确定降低BP 1水平导致生长抑制或细胞凋亡，BP 1表达将减少乳腺癌细胞系使用遗传和药理学方法。本研究因此，将结合联合收割机临床和遗传学方法来确定 BP 1表达在乳腺癌中的重要性。