Involvement of a Novel Rho GTPase Activating Protein in Breast Tumorigenesis
Abstract
We had previously shown that expression of a novel transcript that had sequence similarity to rat Rho GAP sequence was altered in breast carcinoma cell lines. We believed that the putative Rho GAP is functionally active. Rho family of proteins shares homology with the Ras super family. Our working hypothesis was that breast carcinoma where Ras mutations have not been detected could still arise from aberrant Ras signaling by virtue of loss of activity of members of Rho family or factors/proteins that affect the activity of Rho proteins. We have bacterially expressed the putative Rho GAP and shown it to have specificity toward RhoA. To further associate the biochemical activity with its well-established physiological role we have demonstrated that transfected Rho GAP can alter actin organization of fibroblast cell lines. We have transfected breast cancer cells with RhoGAP expression construct and shown it to suppress cell growth. This growth suppression pathway is mediated via p2 1. To better characterize the physiological significance of RhoGAP we have used the yeast two-hybrid system to isolate interacting proteins. The protein was shown to interact with alpha tubulin, TAX1 binding protein, SWI/SNF and HMG CoA reductase. These interactions provide a mechanism for statin induced inhibition of breast carcinoma cells and indicate as yet uncharacterized involvement of RhoGAP in other processes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA420334
Entities
People
- Rajendra P. Kandpal
Organizations
- Fordham University