Tumor Suppressor In Colon Research Articles

CHMP1A expression and function in colon tumors

CHMP1A (Charged multivesicular protein 1A) is a member of the ESCRT‐III family that functions in endosome mediated vesicle trafficking and in gene silencing. However, its function in colon tumors has not been reported. Our preliminary data indicates that CHMP1A might function in tumor development since CHMP1A knockout mice exhibited abnormalities in colon tissue. CHMP1A expression and localization was studied in normal and tumor cells and it is inconclusive at this time. However, CHMP1A mRNA is slightly reduced in colon tumors compared to corresponding normal tissues in a human cancer array. CHMP1A showed diffuse expression including the nucleus of the colon tumor compared to normal tissues which showed no nuclear expression. In addition, knockdown of CHMP1A in normal and tumor cells caused an increase in growth compared to the control cells. Collectively, these results are in agreement with our preliminary data indicating CHMP1A is a tumor suppressor in colon. Supported by NIH Grant 5P20RR016477 to the West Virginia IDeA Network for Biomedical Research Excellence

C/ebpδ Null Mouse as a Model for the Double Knock-out of slc5a8 and slc5a12 in Kidney

slc5a8 and slc5a12 represent the high affinity and low affinity Na+/lactate co-transporters, respectively, in the kidney. Here we show that these transporters are expressed in the apical membrane of the proximal tubular cells in mouse kidney, indicating that these transporters are likely to mediate the first step in the renal reabsorption of lactate. Interestingly, the renal expression of both transporters is almost completely ablated in mice homozygous for the deletion of the transcription factor c/ebpdelta. This effect is tissue-specific since the expression of the transporters is not affected in non-renal tissues. The functional role of C/EBPdelta in the expression of SLC5A8 and SLC5A12 is demonstrable in HEK293 cells in reporter assays using gene-specific promoters. The ablation of the transporters in the kidney is accompanied by a marked increase in urinary excretion of lactate as well as a decrease in blood levels of lactate in c/ebpdelta-/- mice. These data provide evidence for an obligatory role for slc5a8 and slc5a12 in the renal absorption of lactate. In addition, we show that urinary excretion of urate is significantly elevated in c/ebpdelta-/- mice even though the expression of URAT1, the transporter responsible for the apical membrane uptake of urate in renal proximal tubule, is not altered. These data provide in vivo evidence for the functional coupling between lactate reabsorption and urate reabsorption in the kidney. Thus, the fortuitous double knock-out of slc5a8 and slc5a12 in kidney in c/ebpdelta-/- mice reveals the physiologic role of these transporters in the renal handling of lactate and urate.

Application of methylation changes in a novel colon tumor suppressor gene, RASSF2, to tumor marker

Application of methylation changes in a novel colon tumor suppressor gene, RASSF2, to tumor marker