PC CELL DERIVED GROWTH FACTOR IN HUMAN BREAST CANCER

描述（改编自摘要）：这是一个修改后的应用程序， 寻求4年纯化支持的经验丰富的研究者， PC细胞衍生生长因子受体的克隆和鉴定 （PCDGF-R）。PI最近将PCDGF鉴定为一种新的自分泌生长因子 在人乳腺癌细胞（HBCC）系和上皮细胞中过表达 ER-/PR-浸润性导管癌细胞预后差。主要研究者有 显示PCDGF表达受雌激素刺激，并介导雌激素的 促有丝分裂作用，并且PCDGF过表达参与了 从雌激素依赖到独立的乳腺癌， 恶性肿瘤此外，ER-HBCC中PCDGF表达的抑制导致 抑制体内肿瘤形成。PCDGF是一种新的候选药物， 基于抑制其表达或作用的抗乳腺癌治疗。的 生长因子与其受体的相互作用是 调解其行动。本申请提出表征所述新颖的 PCDGF-R。为此，PI最近隔离了一条HBCC线路， 在MCF-7和MDA-MB-468中观察到的PCDGF-R数量的10倍过表达 细胞生物化学、分子学和免疫学方法的组合， 提出了第一步是纯化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cDNA文库。第二种方法将使用 将PCDGF-R cDNA表达克隆到PCDGF-R阴性CHO细胞中。抗 然后将开发阻断PCDGF作用的PCDGF-R单克隆抗体。 基本原理是使用这些抗体来抑制人类乳腺癌的生长 in vivo. PI指出，这些研究具有创新性，因为它们将 提供了一种新的生长因子受体的信息 参与乳腺癌向雌激素非依赖状态的进展。 它们还将为乳腺发育提供分子靶点， 阻断生长因子-受体相互作用的癌症疗法。

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.