Disease relevance of ACVR2A

• CONCLUSIONS: ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene [1].
• Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs [1].
• Using reverse transcriptase-polymerase chain reaction and Southern blot analysis, the mRNA levels of alpha, betaA and betaB subunits and activin receptor type IIA and IIB were analyzed in normal OSE and the ovarian cancer cell line, OVCAR-3 cells [2].
• Because prostate tumors appear to have a high incidence of MSI, we analyzed prostate cancer cell lines, with and without MSI, for ACVR2 and TGFbetaR2 mutations [3].
• Two 8-bp polyadenine tracts of the ACVR2 gene are targets for inactivating frameshift mutations in gastrointestinal neoplasms having microsatellite instability (MSI) [4].

High impact information on ACVR2A

• The frequency of frameshift mutations in coding mononucleotide repeats was significantly lower in MSI-H IBDNs than in sporadic MSI-H CRCs for TGFBR2 (7 of 14 vs 34 of 43 samples; P = .047) and ACVR2 (3 of 14 vs 25 of 43 samples; P = .029) [5].
• We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors [1].
• METHODS: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A(8) tracts (exon 3 and 10) of ACVR2 and the A(10) tract of transforming growth factor beta receptor 2 (TGFBR2) [1].
• The effect of ACVR2 restoration on cell growth, SMAD phosphorylation, and global molecular phenotype was then evaluated [6].
• Activin type II receptor restoration in ACVR2-deficient colon cancer cells induces transforming growth factor-beta response pathway genes [6].

Biological context of ACVR2A

• Decreased cell growth was observed in wt-ACVR2 transfectants relative to ACVR2-deficient vector-transfected controls [6].
• The activin type II receptor (ACVR2) gene is a putative tumor suppressor gene that is frequently mutated in microsatellite-unstable colon cancers (MSI-H colon cancers) [6].

Other interactions of ACVR2A

• For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B) [7].
• ACVR2 is a member of the transforming growth factor (TGF)-beta type II receptor (TGFBR2) family and controls cell growth and differentiation [6].
• However, no difference was observed in levels of betaB subunit, or in activin receptor type IIA and IIB mRNAs following activin treatments in OVCAR-3 cells [2].
• Of 44 amplifiable MSI-H Dukes B2 tumors, 70% harbored TGFBR2, 63% BAX and only 4.5% ACVR2 mutations [8].
• CONCLUSIONS: The present data suggest that the disruption of the transforming growth factor-beta super-family signaling pathway by the alteration of the ACVR2 and/or TGFbetaRII genes and the disruption of antiproliferative function by the PTHLH gene alteration contribute to the development of early colorectal cancer [9].

Analytical, diagnostic and therapeutic context of ACVR2A

• ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein [1].

References