TY - JOUR
T1 - Zonal heterogeneity for gene expression in human pancreatic carcinoma
AU - Nakamura, Toru
AU - Kuwai, Toshio
AU - Kitadai, Yasuhiko
AU - Sasaki, Takamitsu
AU - Fan, Dominic
AU - Coombes, Kevin R.
AU - Kim, Sun Jin
AU - Fidler, Isaiah J.
PY - 2007/8/15
Y1 - 2007/8/15
N2 - Using Affymetrix HG-U133 Plus 2.0 array and laser capture microdissection techniques, we determined whether different zones of the same pancreatic tumor exhibited differential expression of genes. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Three weeks later when tumors were 7 to 9 mm in diameter, gene expression patterns in tumor cells within the central and peripheral zones were compared, and 1,222 genes showed statistically significant differences. Bioinformatic functional analysis revealed that 346 up-regulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IKB kinase/nuclear factor-κB cascade; 876 upregulated genes in the central zone were related to regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathways, response to stress, small GTPase-mediated signal transduction, hexo se metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. The reliability of the microarray results were confirmed by in situ hybridization analysis of the expression of two genes. Collectively, the data showed zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles is essential if microarray analyses of genetic profiles are to produce reproducible data, predict disease prognosis, and allow design of specific therapeutics.
AB - Using Affymetrix HG-U133 Plus 2.0 array and laser capture microdissection techniques, we determined whether different zones of the same pancreatic tumor exhibited differential expression of genes. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Three weeks later when tumors were 7 to 9 mm in diameter, gene expression patterns in tumor cells within the central and peripheral zones were compared, and 1,222 genes showed statistically significant differences. Bioinformatic functional analysis revealed that 346 up-regulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IKB kinase/nuclear factor-κB cascade; 876 upregulated genes in the central zone were related to regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathways, response to stress, small GTPase-mediated signal transduction, hexo se metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. The reliability of the microarray results were confirmed by in situ hybridization analysis of the expression of two genes. Collectively, the data showed zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles is essential if microarray analyses of genetic profiles are to produce reproducible data, predict disease prognosis, and allow design of specific therapeutics.
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U2 - 10.1158/0008-5472.CAN-07-0874
DO - 10.1158/0008-5472.CAN-07-0874
M3 - Article
C2 - 17699763
AN - SCOPUS:34548019460
SN - 0008-5472
VL - 67
SP - 7597
EP - 7604
JO - Cancer Research
JF - Cancer Research
IS - 16
ER -