RASSF1A deficiency profoundly enhanced the development of K-RAS-driven lung tumors <i>in vivo</i> Analysis of these tumors showed loss of RASSF1A-uncoupled RAS from the proapoptotic Hippo pathway as expected.
Using stable clones of two human lung tumor cell lines (NCI-H1792 and NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we show that activated Rheb stimulates the Hippo pathway, but is suppressed in its ability to stimulate the TOR pathway.
Collectively, our results indicated that RASSF1 acts to restrict EMT and invasion by indirectly controlling YAP nuclear shuttling and activation through a RhoB-regulated cytoskeletal remodeling process, with potential implications to delay the progression of RASSF1-hypermethylated lung tumors.
RASSF1A, a candidate tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is frequently inactivated by hypermethylation of its promoter region in a number of malignancies.
We first identified potential transcriptionally important CpG sites using the methylation-specific oligonucleotide array in relation to mRNA expression of RASSF1A and BLU genes in primary lung tumors.
Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers.
In this study, we analyzed promoter methylation in the ras-association domain isoform A (RASSF1A) and the death-associated protein kinase (DAPK) genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region.
H1299 lung cancer cells, lacking Fhit, Wwox, p16(INK4a) and Rassf1a expression due to epigenetic modifications, were used to assess efficacy of epigenetically targeted protocols in suppressing growth of lung tumors, by injection of 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299 tumors.
The human Ras association domain family 1A gene (RASSF1A), recently cloned from the lung tumor locus at 3p21.3, was shown to be frequently inactivated by hypermethylation of its promoter region in a number of malignancies.
The newly identified 3p21.3 tumour suppressor gene RASSF1A is methylated in the majority of primary lung tumours, lung tumour cell lines and in a variable percentage of breast tumours.
The newly identified 3p21.3 tumour suppressor gene RASSF1A is methylated in the majority of primary lung tumours, lung tumour cell lines and in a variable percentage of breast tumours.
The Ras association domain family 1 (RASSF1) gene cloned from the lung tumor suppressor locus 3p21.3 consists of two major alternative transcripts, RASSF1A and RASSF1C.
The human Ras association domain family 1A gene (RASSF1A), recently cloned from the lung tumor suppressor locus 3p21.3, was shown to be hypermethylated in primary lung tumors, and reexpression of RASSF1A suppressed the growth of lung cancer cells (R. Dammann et al., Nat.Genet., 25: 315-319, 2000).