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Title: Regulation and function of the novel candidate tumor suppressor Gene Dlec1 in the HCT116 colorectal cancer cell line
Authors: YUN TONG
Keywords: Dlec1, HCT116, colorectal, cancer
Issue Date: 30-Sep-2009
Citation: YUN TONG (2009-09-30). Regulation and function of the novel candidate tumor suppressor Gene Dlec1 in the HCT116 colorectal cancer cell line. ScholarBank@NUS Repository.
Abstract: DLEC1 (deleted in lung and esophageal cancer 1) is located at 3p22-p21.3 and encodes for a 1755-amino acid polypeptide (Rauch et al., 2006; Daigo et al., 1999). It is a novel candidate tumor suppressor gene that markedly suppressed colony formation in cancer cell lines and reduced tumorigenesis in nude mice (Daigo et al., 1999; Kwong et al., 2006; Qiu et al., 2008). It was frequently down-regulated by promoter hypermethylation and histone hypoacetylation in cancer cell lines (Kwong et al., 2006; Qiu et al., 2008; Seng et al., 2008). The exact biologic function is still unclear and the predicted amino acid sequence of DLEC1 has no significant homology to any of the known proteins or peptides (Daigo et al., 1999). This study was aimed to provide some knowledge regarding the regulation and function of DLEC1 in colorectal cancer. In HCT116 cell line, the PI3K-AKT-mTOR, JNK-SAPK, Ras-Raf-MEK-ERK pathways are constitutively activated. To study the possible mechanism of regulation of DLEC1 by these signaling pathways, RT-PCR was performed to screen for potential drugs that could alter DLEC1 expression. U0126, a specific MEK inhibitor, was shown to be able to up-regulate DLEC1 in a dose-dependent manner. Transient over-expression of DLEC1 as well as treatment using U0126 both suppressed cell proliferation in HCT116 cells. The growth suppressing effect of DLEC1 was confirmed by anchorage dependant colony formation assay. Stable clones of HCT116 expressing DLEC1 showed increased G1 cycle arrest, implying that the inhibitory effect of DLEC1 on cell growth and survival may be caused by G1 arrest. To study the possible mechanism involved, we screened for the expression levels of potential downstream effectors of DLEC1, and found that the transcription factor AP2a2 has been up-regulated in DLEC1 over-expressing stable cell lines. Together, our data suggested that DLEC1 is suppressed by Ras-Raf-MEK-ERK pathway in HCT116 cell line; it has growth inhibitory effect on HCT116 cells,and the possible mechanism involved may be G1 cell cycle arrest, which was contributed by the up-regulation of the transcription factor, AP2a2.
Appears in Collections:Master's Theses (Open)

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