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Erschienen in:
01.08.2010 | Translational Research and Biomarkers
Epigenetic Inactivation of the Thyroid Hormone Receptor β1 Gene at 3p24.2 in Lung Cancer
Erschienen in: Annals of Surgical Oncology | Ausgabe 8/2010
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Background
Frequent allelic loss on chromosome 3p in various human cancers suggests the presence of tumor suppressor genes in this region. The thyroid hormone receptor β1 (TRβ1) gene is located at 3p24.2, where allelic loss frequently occurs in lung cancer, and aberrant TRβ1 methylation was observed in several human cancers.
Methods
We examined the expression, mutation, and promoter methylation of TRβ1 in 18 small cell lung cancer (SCLC) and 29 non-small cell lung cancer (NSCLC) cell lines by reverse-transcription polymerase chain reaction (RT-PCR), direct sequencing, or methylation-specific PCR. Four lung cancer cell lines lacking TRβ1 expression were treated with 5-aza-2-deoxy-cytidine and/or trichostatin-A, and the TRβ1 expression was determined by RT-PCR. We also examined the TRβ1 methylation in 116 NSCLC surgical specimens and analyzed the correlation between methylation status and clinicopathological parameters or mutations of KRAS and EGFR.
Results
TRβ1 expression was absent in 61% of SCLCs and 48% of NSCLCs, and 67% of SCLCs and 45% of NSCLCs carried TRβ1 promoter methylation, while no somatic mutation was found in all cell lines. TRβ1 methylation status was significantly associated with loss of TRβ1 expression. TRβ1 expression was restored by treatment with 5-aza-2-deoxy-cytidine and/or trichostatin-A in four cell lines. TRβ1 methylation was found in 47% of NSCLC surgical specimens; however, the methylation was not significantly associated with any clinicopathological parameters or mutations of KRAS and EGFR.
Conclusions
This is the first study to demonstrate epigenetic inactivation of TRβ1 through aberrant methylation in lung cancer, while TRβ1 mutations are not common in lung cancer.