Conserved transcription factor binding sites of cancer markers derived from primary lung adenocarcinoma microarrays.
Gene transcription in a set of 49 human primary lung adenocarcinomas and 9 normal lung tissue samples was examined using Affymetrix GeneChip technology. A total of 3442 genes, called the set M AD, were found to be either up- or down-regulated by at least 2-fold between the two phenotypes. Genes assigned to a particular gene ontology term were found, in many cases, to be significantly unevenly distributed between the genes in and outside M AD. Terms that were overrepresented in M AD included functions directly implicated in the cancer cell metabolism. Based on their functional roles and expression profiles, genes in M AD were grouped into likely co-regulated gene sets. Highly conserved sequences in the 5 kb region upstream of the genes in these sets were identified with the motif discovery tool, MoDEL. Potential oncogenic transcription factors and their corresponding binding sites were identified in these conserved regions using the TRANSFAC 8.3 database. Several of the transcription factors identified in this study have been shown elsewhere to be involved in oncogenic processes. This study searched beyond phenotypic gene expression profiles in cancer cells, in order to identify the more important regulatory transcription factors that caused these aberrations in gene expression.
Yap
Yee Leng
YL
HKU-Pasteur Research Centre Dexter H.C. Man Building, 8 Sassoon Road Pokfulam, Hong Kong, China. daniely@hkusua.hku.hk
Lam
David C L
DC
Luc
Girard
G
Zhang
Xue Wu
XW
Hernandez
David
D
Gras
Robin
R
Wang
Elaine
E
Chiu
S W
SW
Chung
Lap Ping
LP
Lam
W K
WK
Smith
David K
DK
Minna
John D
JD
Danchin
Antoine
A
Wong
Maria P
MP
D024506:5' Flanking Region; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000378:metabolism; D017124:Conserved Sequence; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D014157:Transcription Factors