PC CELL DERIVED GROWTH FACTOR IN HUMAN BREAST CANCER

描述(改编自摘要)：这是一个由 经验丰富的调查员寻求4年的净化支持， PC细胞源性生长因子受体基因的克隆与鉴定 (PCDGF-R)。PI最近发现PCDGF是一种新的自分泌生长因子 人乳腺癌细胞(HBCC)及其上皮中高表达 ER-/PR-浸润性导管癌细胞预后较差。少年派有 研究表明，PCDGF的表达受雌激素的刺激并介导雌激素的 有丝分裂作用，PCDGF的过度表达参与了这一过程 乳腺癌从雌激素依赖到独立性，这是 恶毒。此外，抑制PCDGF在ER-HBCC中的表达导致 抑制体内肿瘤的形成。PCDGF是小说的候选者 基于抑制其表达或作用的抗乳腺癌治疗。这个 生长因子与其受体的相互作用是 调解它的行动。这项申请旨在刻画这部小说的特征 PCDGF-R为此，PI最近分离了一株HBCC株系 在MCF-7和MDA-MB-468中高表达PCDGF-R的数量是前者的10倍 细胞。生化、分子和免疫学方法的组合是 建议。第一步是纯化PCDGF-R，获得氨基酸序列 将用于合成互补寡核苷酸的信息 筛选人乳腺癌基因文库。第二种方法将使用 PCDGF-R基因在PCDGF-R阴性CHO细胞中的表达克隆抗 随后将开发阻断PCDGF作用的PCDGF-R单抗。 其基本原理是使用这些抗体来抑制人类乳腺癌的生长。 在活体内。国际和平研究所表示，这些研究是创新的，因为它们将 提供有关一种新鉴定的生长因子受体的信息 参与了乳腺癌向雌激素非依赖状态的进展。 它们还将为乳房发育提供分子靶点。 将阻断生长因子-受体相互作用的癌症治疗。

DESCRIPTION (adapted from Abstract): This is a revised application by an experienced investigator seeking 4 years of support for the purification, cloning and characterization of the PC-cell derived growth factor receptor (PCDGF-R). The PI recently identified PCDGF as a novel autocrine growth factor overexpressed in human breast cancer cell (HBCC) lines and in the epithelial cells of ER-/PR- invasive ductal carcinoma with poor prognosis. The PI has shown that PCDGF expression is stimulated by estrogen and mediates estrogen's mitogenic effect, and that PCDGF overexpression is involved in the progression of breast cancer from estrogen dependence to independence, a hallmark of malignancy. Moreover, inhibition of PCDGF expression in ER- HBCC led to inhibition of tumor formation in vivo. PCDGF is a candidate for novel anti-breast cancer therapy based on inhibition of its expression or action. The interaction of a growth factor with its receptor is the initial step in mediating its action. This application proposes to characterize the novel PCDGF-R. For this purpose, the PI recently isolated a HBCC line that overexpresses by 10-fold the number of PCDGF-R seen in MCF-7 and MDA-MB-468 cells. A combination of biochemical, molecular and immunological approaches are proposed. The first one will be to purify PCDGF-R, obtain amino acid sequence information which will be used to synthesize complementary oligonucleotides to screen a human breast cancer cDNA library. The second approach will use expression cloning of PCDGF-R cDNA into PCDGF-R negative CHO cells. Anti PCDGF-R monoclonal antibodies that block PCDGF action will then be developed. The rationale is to use these antibodies to inhibit human breast cancer growth in vivo. The PI states that these studies are innovative since they will provide information on the receptor of a newly characterized growth factor involved in the progression of breast cancer to estrogen independent state. They will also provide a molecular target toward the development of breast cancer therapy that will block growth factor-receptor interaction.