It truly is effectively established that RASSF1 6 have tumor suppres sor activity, and current proof suggests that other members from the loved ones may also function as tumor suppressors. Even though RASSF2 is structurally related to the beer characterized RASSF1A, the mechanisms by which these two loved ones advertise cell death may possibly dier as RASSF2 localizes predominantly towards the nucleus whereas RASSF1A is uncovered largely in the cytoplasm. RASSF2 binds to K Ras within a GTP dependent method and may serve as a K Ras specic eector as it types an endogenous complicated with K Ras. RASSF2 has no apparent intrinsic enzymatic activity or DNA binding properties and therefore acts by interacting with other proapoptotic eectors and tumor suppressors, which includes PAR 4 as well as MST1 2 kinases, therefore regulating the pathways these eectors management. Like RASSF1A, RASSF2 is inactivated inside a variety of tumors by promoter methylation.
RASSF2 has the properties of the tumor suppressor in that its overexpression promotes apoptosis and cell cycle arrest in vitro and inhibits tumor cell development and tumor xenograft formation in nude mice. Conversely, reduction of RASSF2 expression effects in selelck kinase inhibitor enhanced development in soft agar and transformation. Reduction of RASSF2 may possibly also market metastasis. RASSF2 may possibly function in further biological processes apart from apoptosis and development sup pression as advised by RASSF2 knockout mice. These mice produce commonly for the rst two weeks right after birth, exactly where just after they build development retardation and die approximately four weeks immediately after birth. On top of that, these mice develop systemic lymphopenia and altered bone advancement. This suggests that RASSF2 has vital functions in early publish natal improvement and even further conrms that RASSF2 has functions distinct from RASSF1A as RASSF1A knockout mice create usually.
While RASSF2 is expressed inside a broad number of tissues, its expression is relatively tissue specic, with the highest ranges detected in brain, peripheral blood, and lung. RASSF2 is usually downregulated in lung cancer with inactivation of RASSF2 staying more prevalent in NSCLC than selleck SCLC. K Ras is commonly mutated in lung cancer, and inactivation of RASSF2 enhances the transforming prospective of K Ras in rat kidney cells. Quite a few reports indicate that there is a positive correlation in between K Ras BRAF mutations and RASSF2 methylation in principal tumors. So, inactivation of RASSF2 confers a growth advantage to tumor cells harboring activated K Ras, and loss of RASSF2 expression may perhaps be a critical event in Ras mediated transformation. To date, the majority of scientific studies examining the eects of RASSF2 around the transformed phenotype rely on overexpres sion assays, which despite the fact that supplying practical information, have some drawbacks in that overexpression of proteins from viral promoters may yield expression levels far over physiological amounts, therefore producing information that could not be physiologically relevant.