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Epigenetic regulation of RhoB loss of expression in lung cancer.
- Source :
-
BMC cancer [BMC Cancer] 2007 Nov 30; Vol. 7, pp. 220. Date of Electronic Publication: 2007 Nov 30. - Publication Year :
- 2007
-
Abstract
- Background: RhoB is down-regulated in most lung cancer cell lines and tumor tissues when compared with their normal counterparts. The mechanism of this loss of expression is not yet deciphered.<br />Methods: Since no mutation has been reported in the RhoB sequence, we investigated the epigenetic regulation of RhoB expression by analyzing the effect of HDAC inhibitors and methyltransferase inhibitors, by direct sequencing after bisulfite treatment and by methylation specific PCR.<br />Results: We first showed that histone deacetylase (HDAC) inhibitors induce a significant RhoB re-expression in lung cancer cell lines whereas only a slight effect was observed with methyl transferase inhibitors. As promoter methylation is the most common epigenetic process in lung cancer, we performed methylation specific PCR and sequence analysis after bisulfite treatment and demonstrated that RhoB was methylated neither in lung cancer cell lines nor in tumor tissues. We also showed that a variable number of tandem repeats sequences in the 5' region of the RhoB gene was involved in HDAC response.<br />Conclusion: We thus propose that RhoB regulation of expression occurs mainly by histone deacetylation rather than by promoter hypermethylation and that this process can be modulated by specific 5' sequences within the promoter.
- Subjects :
- Azacitidine analogs & derivatives
Azacitidine pharmacology
Base Sequence
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor chemistry
Cell Line, Tumor metabolism
Cell Line, Tumor pathology
DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors
DNA Methylation
Down-Regulation
Enzyme Inhibitors pharmacology
Gene Expression
Gene Silencing
Histone Deacetylase Inhibitors
Humans
Immunoblotting
Lung Neoplasms metabolism
Lung Neoplasms pathology
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Sulfites
Tandem Repeat Sequences
rhoB GTP-Binding Protein genetics
Carcinoma, Non-Small-Cell Lung genetics
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Lung Neoplasms genetics
rhoB GTP-Binding Protein biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 18047684
- Full Text :
- https://doi.org/10.1186/1471-2407-7-220