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        Microarray Approaches for Analysis of Tumor Suppressor Gene Function

        互联网

        660
        Many tumor suppressor genes are known to function at least in part through regulation of the transcription of downstream effector genes (Table 1 ). A major example of such a transcriptional regulator is p53, one of the most commonly mutated tumor suppressor genes in human cancer (1 ) and hence one of the most exhaustively studied. Estimates based on a survey of p53 binding sites in the genome put the number of p53-regulated genes at several hundred (2 ), while the finding that p53 can affect the expression of some genes in the absence of direct DNA binding may increase this number (3 ). Genes known to be regulated by p53 play roles in many important cellular processes, including cell cycle progression, DNA repair, and apoptosis (Table 2 ). Loss of such a tumor suppressor gene can disrupt the regulation of multiple genes, affecting numerous cellular pathways and leading to a variety of phenotypic changes. Comparative analysis of complex patterns of gene expression can therefore provide a powerful tool to develop insight into mechanisms of tumor suppressor gene function involving transcriptional regulation.
        Table 1  Tumor Suppressor Genes That Can Act as Transcription Factors

        TP53

        Tumor protein p53

        WT1

        Wilm’s tumor 1

        VHL

        Von Hippel-Lindau syndrome

        MEN1

        Multiple endocrine neoplasia, type 1

        TCF7

        Transcription factor 7

        MXI1

        MAX-interacting protein 1

        BRCA1

        Breast cancer 1, early onset

        BRCA2

        Breast cancer 2, early onset

        ATM

        Ataxia telangiectasia

        NBL1

        Neuroblastoma candidate region, suppression of tumorigenicity 1

        NME1

        Nonmetastatic cells 1, protein expressed in

        EGR1

        Early growth response 1

        Table 2  Examples of Tp53 Effector Genes with Roles in Cellular Stress Processes

        Cell Cycle Control

        Apoptosis

        DNA Repair

        Other

        CIP1/WAF1

        BAX

        XPC

        MDM2

        ClnG

        BCL-X

        DDB2

        FRA1

        ClnD1

        PAG608

        GADD45A

        ATF3

        WIP1

        FAS/APO1

        PCNA

        14-3-3 σ

        EGF-R

        KILLER/DR5

         

        Rb

        TGF-α

        TRUNDD

         

        c-MYC

        Rb

        TRID

         

        MMP2

        PCNA

        seven in absentia

         

        MAP4

        GADD45A

        IGF-BP3

         

        TSP1 & 2

        14-3-3 σ

        PIG1 to PIG14

         

        BAI-1

        BTG2

           

        WIG1

        seven in absentia

           

        amyloid

        IGF-BP3

           

        GML

        PIG1 to PIG14

           

        bFGF

        inhibin-β

           

        PIR121

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