Lef/Tcf Full Length Expression And Their Isoforms Vary

1752 WordsFeb 27, 20178 Pages
LEF/TCF full length expression and their isoforms vary between normal cells and colon cancer cells. In the normal colon, TCF-1 and TCF-4 are expressed and LEF-1 and TCF-3 are silenced.[43], [45],[ Moreover they also have different biological roles. In general LEF-1 is viewed as an activator and TCF-3 as mostly a repressor but can be a activator ([39]; [40]). Both TCF-1 and TCF-4 act as both inhibitors and activators, but TCF-4 is the dominant interactor of β -catenin in the colon. TCF4 mediates the transformative process of colon epithelial cells when tumor-suppressor protein adenomatous polyposis coli (APC) is loss. The family of proteins has also been found to regulate one another. For example, transcription of LEF-1 can be directly…show more content…
It also has been shown that cyclin D1 is a downstream target of the β-catenin–TCF complex and therefore when continually activated allows cells to proceed through cell cycle and continue tumor growth. In support of this, expression of the dominant-negative form of TCF, lacking the β-catenin binding domain, in colon-cancer cells strongly inhibits expression of cyclin D1 causing cells to arrest in the G1 phase of the cell cycle due to the lack of activation of cyclin D1 [23]). The β-catenin/LEF-1 pathway also shows cyclin D1 as a direct target; LEF-1 binds directly in the cyclin D1 promoter [22]. In addition, anti-sense cyclin D1 cDNA inhibits growth of SW480 colon cancer cells in nude mice; this suggests a critical role for cyclin D1 in tumorigenesis and that targeting the TCF/LEF family can downregulate its specific activity [49]. The end point of the cell cycle is mitosis; this is when one cell becomes two. Several studies have shown that TCF-4 maintains the crypt stem cells of the gut and its continuous activation causes uncontrolled cell proliferation[50]). In support of this finding, another lab determined the disruption of β-catenin/TCF-4 complex resulted in decreasing the expression of c-MYC and downstream targets causing G1 arrest ([9]). TCF-4 may be an important switch in cell cycle regulation and proliferation and when constitutively activated a monumental event in colon cancer tumorigenesis. Figure 3. Role of TCF/LEF in metastasis: a. Adhesion The

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