Tyrosine Kinase Receptors Signaling Revealed by Global Expression Profiles: Implications for Cancer Biology

R.   M.   Melillo; Massimo      Santoro

Abstract

Increasing numbers of human diseases involve mutations, misexpression or malfunctioning of receptor protein tyrosine kinases (RTK). In particular, human cancers are often characterized by altered RTK function, due to different genetic causes. Identification of the gene expression program triggered by (RTKs) is essential to clarify the molecular basis of their biological activities. Intracellular signals of RTKs are initiated by specific tyrosines which, when autophosphorylated, recruit signal transducers. How the activation of different signaling pathways is translated into a certain pattern of gene expression is currently unknown. Recently, scientists have tried to answer this question applying DNA microarrays technology using wild-type and mutant RTKs transiently stimulated with their cognate growth factors. The transcriptional response to chronic stimulation of cells upon ectopic expression of oncogenic RTKs has also been investigated through DNA microarrays. The results obtained recently in this field, with their possible implication in cancer development and their impact on cancer diagnosis and treatment will be discussed.

Keywords: RTK, oncogene, gene expression profiling, thyroid

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