Analysis of the Role of Cortactin in Tumor Cell Invasion
Abstract
Cortactin is a prominent substrate of protein tyrosine kinase Src and is frequently amplified and overexpressed along with the chromosome 11q13 in breast cancer. In vitro and in vivo, cortactin binds to and cross-links filamentous actin (F-actin). The F-actin cross-linking activity of cortactin is down-regulated by Src, resulting in increase in dynamics of actin cytoskeleton. We hypothesize that cortactin is implicated in tumorigenesis by promoting metastasis. To test this hypothesis, we developed several retroviruses encoding cortactin variants and infected the viruses into MDA-MB-231 cells. The cells overexpressing wild type cortactin exhibited increase in the motility as analyzed by a Trans-well apparatus, whereas cells overexpressing a cortactin mutant deficient in tyrosine phosphorylation reduced cell motility. We also examined these cells with an in vivo metastasis model in which cortactin overexpressors were injected into the left cardiac ventricle of female nude mice to develop lesions in bone. The preliminary data showed that overexpression of wild-type cortactin increases in metastases of MDA-MB-231 cells in bone and cachexia, whereas cells overexpressing a cortactin mutant deficient in tyrosine phosphorylation showed an impaired capacity to induce osteolytic metastases and cachexia. Furthermore, mice injected with the cells expressing the cortactin mutant tend to have longer life span compared to mice injected with wild-type cortactin transfected cells. These results suggest that tyrosine phosphorylation of cortactin plays an important role in the osteolytic metastases of human breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA389850
Entities
People
- Xi Zhan
Organizations
- American Red Cross