Open AccessHistone deacetylation is directly involved in desilencing the expression of the catalytic subunit of telomerase in normal lung fibroblast
Author(s) -
Mukhopadhyay N.K.,
Gordon G.J.,
Maulik G.,
Doerre G.,
Liu Brian C.S.,
Bueno R.,
Sugarbaker D.J.,
Jaklitsch M.T.
Publication year - 2005
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2005.tb00496.x
Subject(s) - telomerase , trichostatin a , telomerase reverse transcriptase , microbiology and biotechnology , biology , histone , fibroblast , protein subunit , downregulation and upregulation , cancer research , cell culture , chemistry , histone deacetylase , biochemistry , dna , gene , genetics
The regulation of telomerase expression in normal cells is poorly understood. Moreover, the molecular mechanism underlying tumor‐specific expression of telomerase remains unclear. We investigated the link between histone deacetylation and telomerase activity in normal lung and lung tumor cells. Four non‐small‐cell lung cancer (NSCLC) lines and one normal lung fibroblast line were tested for telomerase activity with or without Trichostatin A (TSA). The telomerase activity and the expression of telomerase associated components were determined by TRAP assay, RT‐PCR analysis and Western blot analysis. All 4 NSCLC cell lines exposed to 1μM TSA for 24h had no change in telomerase activity or hTERT mRNA level. Telomerase activity was very low in normal lung fibroblasts (mrc‐9) until exposed to 1μM TSA for 24h, at which time telomerase activity was readily detectable, with concomitant upregulation of hTERT mRNA (10‐fold). The level of other telomerase associated components (hTER and TP1) were unaltered. Furthermore, 1μM TSA exposure for 24h did not alter the level of c‐Myc or p21 mRNA. Immunodetection reveled that hTERT protein expression increased (∼6 fold) compared to c‐Myc, p21, or gelsolin. The effect of TSA on hTERT expression is independent of DNA methylation as judged by 5‐azacytidine (5aza) treatment. TSA effect on mrc‐9 cells is unaltered even in the presence of 200μg/ml cyclohexamide, suggesting a direct inhibition of histone deacetylation. Collectively, our study indicates that inhibition of histone deacetylation selectively regulates the transcriptional derepression of telomerase catalytic subunit in normal lung fibroblast cells compared to lung tumor cells.