Subsequent studies have demonstrated that DLC-1 is generally expressed in normal human tissues as well as in rats, while it always exists inactivated or even lost in many human cancers, which characterizes DLC-1 as a potential tumor suppressor.
Taken together, our results suggest that DLC-1 might be an NPC-related tumor suppressor gene affected by aberrant promoter methylation and gene deletion.
This comparative expression analysis of DLC-1 and -2 identifies down-regulation of the two emerging bona fide tumor suppressor genes in additional types of solid tumors.
However, differential expression of the four DLC1 isoforms is found in tumor cell lines: Isoform 1 (longest) and 3 (short thus probably nonfunctional) share a promoter and are silenced in almost all cancer and immortalized cell lines, whereas isoform 2 and 4 utilize different promoters and are frequently downregulated.
This isoform is functional GAP protein and tumor suppressor and targeting of its expression results in the increase of DLC1 related cell processes: RHO activation and cell migration.
Regardless of the epigenetic mechanism of DLC1 inactivation, SAHA treatment of DLC1-transduced cells had a synergistic inhibitory effect on tumor cell proliferation and tumorigenesis in both cell lines.
In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1.
The aim of this study was to evaluate whether DLC-1, a newly identified tumor-suppressor gene on chromosome 8p22, is involved in the tumorigenesis of MBs and the histologically similar SPNETs.
Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: prospects for gene therapy.
That binding, which interferes with the interaction of RhoA-GTP with the RhoGAP domain, reduces the hydrolysis of RhoA-GTP, the binding of other DLC1 ligands, and the colocalization of DLC1 with focal adhesions and attenuates tumor suppressor activity.
A recent study in Genes & Development by Xue and colleagues (1439-1444) now provides in vivo evidence that DLC1, a negative regulator of Rho, is a tumor suppressor gene deleted almost as frequently as p53 in common cancers such as breast, colon, and lung.
Since DLC‑1 is a candidate tumor suppressor gene, we sought to determine whether DLC‑1 expression is associated with cell proliferation in colon cancer cell lines.
DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers.
To determine whether aberrant methylation is a contributing factor to transcriptional inactivation of DLC-1 (deleted in liver cancer-1), a candidate tumor suppressor gene, we examined its methylation status in twelve hepatocellular carcinoma. breast, colon, and prostate tumor cell lines with low or undetectable expression of DLC-1.
DLC-1 is a multi-domain protein that includes a Rho GTPase activating protein (RhoGAP) domain which has been hypothesized to be the basis of its tumor suppressive actions.
Aberrant DLC1 methylation appeared to be a relatively early event during renal tumorigenesis since 33% of the RCC tumors with pT1 (TNM staging) showed methylation, which is similar to other late stage tumors.
DLC-1 inhibits cell growth and invasion in human colon cancer, functioning as a tumor-suppressor gene, possibly through the regulation of the Wnt/β-catenin signaling pathway.