Identification of Src transformation fingerprint in human colon cancer.
We used a classical rodent model of transformation to understand the transcriptional processes, and hence the molecular and cellular events a given cell undergoes when progressing from a normal to a transformed phenotype. Src activation is evident in 80% of human colon cancer, yet the myriad of cellular processes effected at the level of gene expression has yet to be fully documented. We identified a Src 'transformation fingerprint' within the gene expression profiles of Src-transformed rat 3Y1 fibroblasts demonstrating a progression in transformation characteristics. To evaluate the role of this gene set in human cancer development and progression, we extracted the orthologous genes present on the Affymetrix Hu95A GeneChip (12k named genes) and compared expression profiles between the Src-induced rodent cell line model of transformation and staged colon tumors where Src is known to be activated. A similar gene expression pattern between the cell line model and staged colon tumors for components of the cell cycle, cytoskeletal associated proteins, transcription factors and lysosomal proteins suggests the need for co-regulation of several cellular processes in the progression of cancer. Genes not previously implicated in tumorigenesis were detected, as well as a set of 14 novel, highly conserved genes with here-to-fore unknown function. These studies define a set of transformation associated genes whose up-regulation has implications for understanding Src mediated transformation and strengthens the role of Src in the development and progression of human colon cancer. Supportive Supplemental Data can be viewed at http://pga.tigr.org/PGApubs.shtml.
Malek
Renae L
RL
Department of Functional Genomics, The Institute for Genomic Research, 9712 Medical Center Dr, Rockville, Maryland, MD 20850, USA.
Irby
Rosalyn B
RB
Guo
Qingbin M
QM
Lee
Kerry
K
Wong
Sylvia
S
He
Mei
M
Tsai
Jennifer
J
Frank
Bryan
B
Liu
Edison T
ET
Quackenbush
John
J
Jove
Richard
R
Yeatman
Timothy J
TJ
Lee
Norman H
NH
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016391:Genes, src; D006801:Humans; D011728:Pyridones / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D011728:Pyridones; D011743:Pyrimidines; C410732:PD 180970