Tumor Suppressor Genes pp 141-153

Part of the Methods in Molecular Biology™ book series (MIMB, volume 223) | Cite as

Microarray Approaches for Analysis of Tumor Suppressor Gene Function

  • Sally A. Amundson
  • Albert J. FornaceJr.

Abstract

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

14-3-3σ

EGF-R

KILLER/DR5

 

Rb

TGF-α

TRUNDD

 

c-MYC

Rb

TRID

 

MMP2

PCNA

seven in absentia

 

MAP4

GADD45A

IGF-BP3

 

TSP1 & 2

14-3-3σ

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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Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Sally A. Amundson
    • 1
  • Albert J. FornaceJr.
    • 1
  1. 1.National Cancer InstituteNational Institutes of HealthBethesda

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