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LRIG Cell Surface Receptors In Health and Disease: Molecular, Physiological , and Clinical Studies wit special emphasiz on brain tumours

Research project

Head of project

Project overview

Project period:

2007-01-18 2008-12-31

Funding

Finansår , 2003, 2004, 2005, 2006, 2007, 2008

huvudman: R Henriksson, finansiar: Cancerfonden, y2003: 1200, y2004: 1200, y2005: 1200, y2006: 1200, y2007: 1200, y2008: 1200,

huvudman: H Hedman, finansiar: VR, y2003: , y2004: , y2005: 250, y2006: 250, y2007: 250, y2008: ,

Participating departments and units at Umeå University

Department of Radiation Sciences

Research subject

Cancer

Project description

We have recently cloned the genes for human LRIG1-3, which constitute a gene family and are predicted to encode integral cell membrane proteins with cellular 15 leucine-rich repeats and immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. LRIG1 has been detected in mouse glial cells while, in man, we have shown extensive expression of LRIG1/2, mRNA and proteins in normal tissues and some tumour cells.



The functions of the LRIG-proteins are not known but their structures are suggestive of cell surface receptors. No receptor ligand is known. The LRIG-proteins show structural similarities to the fruit fly Drosophila melanogaster Kekkon proteins, which inhibits EGFR-mediated signaling. We have therefore speculated that LRIG might be modulators of signal transduction pathways in mammalian cells and tumours and, as such, playing important roles in mammalian physiology/ patho-physiology and tumorigenesis. Recently, it was shown that LRIG1 knock-out mice developed psoriasis-like lesions with hyperproliferation of a subset of keratinocytes, consistent with our hypothesis that LRIG1 is a suppresor of growth factor receptor-mediated signaling. Our early clinical studies support that LRIG1 has a role in malignant processes. We will therefore deepen our evaluation regarding the molecular, physiological, and developmental functions of the mouse and human LRIG proteins as well as delineating possible role in cancer and in other diseases with known defects in growth factor signalling.