FIBRONECTIN RECEPTORS AND CARCINOMA PROGRESSION

描述：申请人已鉴定β 6亚基，并显示 与α V形成异源二聚体，并作为纤连蛋白受体发挥功能。 此外，其表达仅限于上皮细胞，并且显著增加， 在发育、伤口愈合、炎症和恶性肿瘤期间， 转型 最大的α v β 6的表达被发现在侵袭性 并且申请人已经发现转染β 6 结肠癌细胞在胶原蛋白凝胶中的增殖。 基于这些数据，他假设alphavbeta 6在 在体内癌细胞的侵袭性生长中。 为了验证这一 假设，他将研究癌细胞从新鲜的组织中迁移出来， 将肿瘤植入三维胶原纤维连接蛋白基质中。 他 将在这些条件下检查α v β 6的分布， 确定抗α v β 6抗体是否干扰迁移。 他 然后将描述一系列表达癌基因的小鼠品系， c-neu、c-src和多瘤中T在小鼠乳腺肿瘤控制下的作用 病毒启动子 α v β 6在这些肿瘤组织中的分布 将分析小鼠并将其与癌基因中的肿瘤进展相关联 表情 最后，这些产生β 6阳性肿瘤的小鼠将被 与β 6缺失小鼠杂交，以确定肿瘤中是否存在某些差异， 观察细胞行为。

DESCRIPTION: The applicant has identified the beta6 subunit, showed it forms heterodimers with alphav, and functions as a fibronectin receptor. Moreover, its expression is limited to epithelia and increases dramatically during development, wound healing, inflammation, and during malignant transformation. The largest expression of alphavbeta6 is found at invasive edges of carcinomas, and the applicant has found that transfection of beta6 in to colon cancer cells increases their proliferation in a collagen gel. Based on these data, he hypothesizes that alphavbeta6 plays a critical role in the invasive growth of carcinomas cells in vivo. To test this hypothesis, he will examine the migration of carcinoma cells out of freshly explanted tumors into a three dimensional collagen-fibronectin matrix. He will examine the distribution of alphavbeta6 under these conditions, and determine whether antibodies to alphavbeta6 interfere with migration. He will then characterize a series of mouse lines expressing oncogenes such as c-neu, c-src, and polyoma middle T under control of mouse mammary tumor virus promoter. The distribution of alphavbeta6 in tumor tissue of these mice will be analyzed and correlated with tumor progression in oncogene expression. Finally, these mice that develop beta6 positive tumors will be crossed with beta6 null mice, to determine whether some difference in tumor cell behavior is observed.