Studies of the function of the mammalian disintregrin and cystein domains of adam9 protein by rna silencing technology.

• Grant number: 07/53765-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2007
• End date: October 31, 2008
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Heloisa Sobreiro Selistre de Araújo
• Grantee: David Shaun Buss
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

This study will examine the function of the disintegrin and cysteine-rich domains of mammalian ADAM metalloprotease proteins, especially ADAM9. ADAM9 has recently been implicated in the metastasis of many human tumours, including breast, liver, pancreas, gastric and skin cancers. Human ADAM family proteins are not yet well understood, but have many similarities to the much better characterised metalloproteases found in snake venoms. This laboratory has extensive experience of snake metalloproteases such as Alternagin from Bothrops alternatus, and proposes to build on this large body of knowledge to investigate ADAM9. To this end, the disintegrin/cysteine domains from ADAM9 has already been cloned and expressed in a bacterial system. Disintegrin/cysteine expression in câncer cell lines will be investigated, and the effect of ADAM9 on the expression of important cell signaling factors such as Vascular Endothelial Cell Growth Factor (VEGF) will be determined. The effect on cell adhesion and proliferation will be assessed using well established assays. ADAM9 will be compared to data already obtained for alternagin C. To determine the function of ADAM9 more precisely, a loss-of-function study will be performed by developing an siRNA technique to silence ADAM9 expression in some cancer cell lines. (AU)