THERAPEUTIC TARGETS TO PREVENT BREAST CANCER METASTASIS

预防乳腺癌转移的治疗目标

• 批准号: 6514887
• 负责人: JOSEPH Thomas PENTO
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514887
• 关键词: antisense nucleic acid; athymic mouse; breast neoplasms; complementary DNA; fibroblast growth factor; gene induction /repression; metastasis; microarray technology; neoplasm /cancer genetics; neoplastic process; northern blottings; oligonucleotides; polymerase chain reaction; video microscopy

DESCRIPTION: (Applicant's Description) The results of our studies with Keratinocyte Growth Factor (KGF) and the existing literature indicate that KGF has a rapid and profound influence on breast cancer cell motility. Based on these results, it appears that KGF, secreted from breast stromal tissue, may act as an early signal in tumor cell proliferation and the initiation of metastasis. If this hypothesis is correct, therapeutic inhibition of genes and/or proteins regulated by KGF, should impede the progression of ER-positive breast cancer cells to a metastatic phenotype and make the tumor more manageable by surgery, endocrine therapy or other cytotoxic agents. The central hypothesis, derived from the literature and our previous studies, is that KGF-regulated gene products induce cell scattering motility of human breast cancer cells, which may be an early event in the metastatic progression of primary tumor cells. Using cDNA expression arrays, we have identified a specific group of "Candidate Target Genes", that are up or down regulated by KGF, which may be directly associated with KGF effects on breast cancer cells. The hypothesis to be tested in this proposal is that specific genes, regulated by KGF, are involved in mediating the motility of breast cancer cells. Selective inhibition of individual candidate genes, using antisense oligonucleotides, will be used to demonstrate the involvement of each gene product in KGF induced motility of breast cancer cells in culture and in mouse xenographs in vivo. The results of this study should lead to the identification of important new therapeutic targets and biomarkers involved in breast cancer cell progression and metastatic development. This should result in the development of new therapeutic agents that may be very specific and highly effective inhibitors of breast cancer progression and metastatic spread and/or provide critical new biomarkers for cancer staging and treatment design.

描述：（申请人的描述）我们的研究结果， 角质细胞生长因子（KGF）和现有文献表明，KGF 对乳腺癌细胞的运动有着快速而深远的影响。基于 这些结果表明，乳腺间质组织分泌的KGF可能 作为肿瘤细胞增殖和启动的早期信号， 转移如果这个假设是正确的， 和/或KGF调节的蛋白质，应该阻止ER阳性的进展。 乳腺癌细胞转移表型，使肿瘤更多 可通过手术、内分泌治疗或其他细胞毒性药物治疗。的 从文献和我们以前的研究中得出的中心假设是 KGF调节基因产物诱导人细胞散射运动 乳腺癌细胞，这可能是转移进展的早期事件， 原发性肿瘤细胞。使用cDNA表达阵列，我们已经确定了一个 特定组的“候选靶基因”，其被 KGF，这可能与KGF对乳腺癌细胞的作用直接相关。 在这项提议中要检验的假设是，特定的基因， 通过KGF，参与介导乳腺癌细胞的运动。 选择性抑制个别候选基因，使用反义 寡核苷酸，将被用来证明每个基因的参与 KGF产物诱导乳腺癌细胞运动的实验研究 体内异种移植。 这项研究的结果应导致确定重要的新的 参与乳腺癌细胞进展的治疗靶点和生物标志物 和转移性发展。这将导致开发新的 可以是非常特异和高效的抑制剂的治疗剂 乳腺癌进展和转移性扩散和/或提供关键的新的 用于癌症分期和治疗设计的生物标志物。

项目成果

Influence of KGF on the progression of pancreatic cancer.

• 发表时间: 2009-08
• 期刊: Anticancer research
• 影响因子: 2
• 作者: X. Zang;M. Lerner;D. Brackett;J. Pento

Wilms' tumor 1 protein and focal adhesion kinase mediate keratinocyte growth factor signaling in breast cancer cells.

Wilms 肿瘤 1 蛋白和粘着斑激酶介导乳腺癌细胞中的角质形成细胞生长因子信号传导。

• 发表时间: 2008
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Zang,Xiao-Ping;Pento,JThomas;Tari,AnaM
• 通讯作者: Tari,AnaM

Development of keratinocyte growth factor receptor tyrosine kinase inhibitors for the treatment of cancer.

• 发表时间: 2007-11
• 期刊: Anticancer research
• 影响因子: 2
• 作者: J. Hackett;Zili Xiao;X. Zang;M. Lerner;D. Brackett;R. Brueggemeier;Pui-Kai Li;J. Pento

Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.

• 发表时间: 2002-09
• 期刊: Anticancer research
• 影响因子: 2
• 作者: X. Zang;Thao Nguyen;J. Pento

SiRNA inhibition of ER-alpha expression reduces KGF-induced proliferation of breast cancer cells.

ER-α 表达的 siRNA 抑制可减少 KGF 诱导的乳腺癌细胞增殖。

• 发表时间: 2008
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Zang,Xiao-Ping;Pento,JThomas
• 通讯作者: Pento,JThomas