Gene expression profile in colon cancer cells with respect to XIAP expression status.
OBJECTIVE
We observed a marked synergism between peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and X-linked inhibitor of apoptosis (XIAP) down-regulation in colon cancer. In the current study, we detected the gene expression profile in HCT116 cells treated with or without PPARgamma ligand troglitazone.


METHODS
HCT116-XIAP(+/+) and HCT116-XIAP(-/-) cells were treated with or without 50 microM troglitazone for 48 h. Gene expressions were detected by microarray, and selected genes were validated by reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, and Western blot.


RESULTS
Relative to HCT116-XIAP(+/+) cells, 58 genes were up-regulated and 33 genes down-regulated in HCT116-XIAP(-/-) cells, all by > or =4-fold. These genes could be classified into a wide variety of functional classes, but we focused on those related to angiogenesis, apoptosis, and proliferation. Thus, two pro-apoptotic genes and one pro-proliferation gene were up-regulated in HCT116-XIAP(-/-) cells. Two pro-proliferation genes, one pro-angiogenesis gene, one anti-angiogenesis gene, and one anti-apoptosis gene were down-regulated in HCT116-XIAP(-/-) cells. Relative to HCT116-XIAP(+/+) cells treated with troglitazone, 137 genes were up-regulated, and 31 genes were down-regulated in troglitazone-treated HCT116-XIAP(-/-) cells, all by > or =4-fold. Among the up-regulated genes were two anti-angiogenesis genes, seven pro-apoptosis genes, and six anti-proliferation genes. Among the down-regulated genes were one anti-angiogenesis gene, one pro-angiogenesis gene, one anti-apoptosis gene, one anti-proliferation gene, and two pro-proliferation genes.


CONCLUSIONS
Down-regulation of XIAP in HCT116 cells with or without troglitazone treatment was associated with changes of gene expression that favor increased tendency of apoptosis, decreased cell proliferation, and angiogenesis potential.
Qiao
Liang
L
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
Li
Gloria H Y
GH
Dai
Yun
Y
Wang
Jide
J
Li
Zesong
Z
Zou
Bing
B
Gu
Qing
Q
Ma
Juan
J
Pang
R
R
Lan
Hui Y
HY
Wong
Benjamin C Y
BC
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism
D002839:Chromans; D045162:Thiazolidinediones; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D000077288:Troglitazone