RUNX3 inhibits cell proliferation and induces apoptosis by TGF-beta-dependent and -independent mechanisms in human colon carcinoma cells.
BACKGROUND
Genes involved in the TGF-beta signaling pathway are often altered in several types of cancers. The TGF-beta-resistant human colon cancer cell line HT-29 has inactivated TbetaRII and deficient expression of RUNX3 and Smad4, which are involved in the TGF-beta signaling pathway.


METHODS
Western blot and immunocytochemistry were performed to confirm gene expression, the MTT assay to detect cell growth, flow cytometry to investigate the cell cycle and the TUNEL to detect cell apoptosis.


RESULTS
In the absence of TGF-beta, Bim was upregulated, cell growth was inhibited and apoptosis was induced. TGF-beta treatment did not affect RUNX3 expression; however, the increase in Bim expression was significant and time dependent. Interestingly, Smad4 but not Smad2/3 was also upregulated upon exposure to TGF-beta. This was not the case after TGF-beta treatment of parent HT-29 cells. As expected, TGF-beta further inhibited cell growth and induced apoptosis in HT-29/RUNX3+ cells.


CONCLUSIONS
Our data demonstrate that RUNX3 is involved in TGF-beta-dependent and -independent cell growth inhibition and apoptosis induction pathways.
Tong
Dan-Dan
DD
Department of Pathology, Tumor Hospital, Harbin Medical University, China.
Jiang
Ying
Y
Li
Ming
M
Kong
Dan
D
Meng
Xiang-Nin
XN
Zhao
Yu-Zhen
YZ
Jin
Yan
Y
Bai
Jing
J
Fu
Song-Bin
SB
Geng
Jing-Shu
JS
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D050677:Core Binding Factor Alpha 3 Subunit; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C493729:Runx3 protein, human; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta