Microarray Approaches for Analysis of Tumor Suppressor Gene Function

互联网2014-02-13

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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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