GRB7

Abstract: It has long been postulated that protein tyrosine phosphatases may act as tumor suppressors because of their ability to counteract the oncogenic actions of protein tyrosine kinases. Here we report the cloning and characterization of a novel human protein tyrosine phosphatase, TEP1. TEP1 contains the protein tyrosine phosphatase signature motif, and we show that it possesses an intrinsic protein tyrosine phosphatase activity. TEP1 also shares extensive homology with tensin, a cytoskeletal protein localized to focal adhesions, and with auxilin, a protein involved in synaptic vesicle transport. Immunofluorescence studies show that TEP1 is a cytoplasmic protein. The abundance of TEP1 transcription is altered in many transformed cells. In the transforming growth factor β-sensitive cells, TEP1 expression is rapidly down-regulated by transforming growth factor β, a cytokine shown to be involved in regulating cell adhesion and cell motility. We have also mapped the gene encoding TEP1 to chromosome 10q23, a locus that is frequently deleted in a variety of human cancers. TEP1 protein is identical to the protein encoded by the candidate tumor suppressor gene PTEN/MMAC1. Our functional studies of the TEP1 protein suggest that its tumor suppressor function may associate with its intrinsic protein tyrosine phosphatase activity and its cytoplasmic localization.

Abstract: Epidermal growth factor receptor (EGFR) and its three related proteins (the ERBB family) are receptor tyrosine kinases that play essential roles in both normal physiological conditions and cancerous conditions Upon binding its ligands, dynamic conformational changes occur in both extracellular and intracellular domains of the receptor tyrosine kinases, resulting in the transphosphorylation of tyrosine residues in the C-terminal regulatory domain These provide docking sites for downstream molecules and lead to the evasion of apoptosis, to proliferation, to invasion and to metastases, all of which are important for the cancer phenotype Mutation in the tyrosine kinase domain of the EGFR gene was found in a subset of lung cancers in 2002 Lung cancers with an EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib Here, we review the discovery of EGFR, the EGFR signal transduction pathway and mutations of the EGFR gene in lung cancers and glioblastomas The biological significance of such mutations and their relationship with other activated genes in lung cancers are also discussed

Abstract: This chapter reviews briefly the prevalence of overexpression of the epidermal growth factor receptor in human cancers. In addition, it examines the mechanisms responsible for increased expression and its clinical significance.