갑상선암 세포주와 갑상선암 조직에서 Gelsolin 유전자의 DNA Methylation의 양상 = DNA Methylation of Gelsolin Gene in Thyroid Cancer Cell Lines and Thyroid Cancer Tissues

다국어 초록 (Multilingual Abstract)

Gelsolin is an actin-binding protein involved in dynamic changes of the actin cytoskeleton. The protein regulates the length of actin filaments by binding, severing, and capping the fast-growing filament ends and promotes actin nucleation. Gelsolin is widely expressed in normal tussues. Decreased gelsolin expression occurs in many transformed cell types and in carcinomas of the colon,bladder, breast, lung, stomach, and prostate. Transciptional silencing of tumor suppressor genes by aberrant methylation of CpG islands plays a crucial role in the development of various cancers. Noske et al. showed inactivation of gelsolin might be mediated by epigenetic modification. But there is no information about the relationship between the gelsolin gene and thyroid cancer. We investigated DNA methylation in thyroid cancer cell lines and tissues from papillary thyroid cancer. We performed reverse transcription-polymerases chain reaction with methylation inhibitor 5-aza-2’-deoxycytidine (DAC) treatment and histone deacetylase inhibitor trichostatin A (TSA) treatment in 3 thyroid cancer cell lines, and combined bisulfite restriction analysis in 5 thyroid cancer cell lines and thyroid tissues from 12 papillary thyroid cancers. Almost all thyroid cancer cell lines showed promoter hypermethylation of gelsolin. Gelsolin was not methylated in all of 12 papillary thyroid cancer tissue specimens. DAC and TSA treatment did not increase the expression of gelsolin messenger RNA in thyroid cancer cell lines. These results suggest that DNA methylation of gelsolin does not contribute to thyroid tumor development, especially in papillary thyroid carcinoma.

참고문헌 (Reference)

1 Kim HL, "Using protein expressions to predict survival in clear cell renal carcinoma" (10) : 5464-5471, 2004

2 Shieh DB, "Tissue expression of gelsolin in oral carcinogenesis progression and its clinicopathological implications" (42) : 599-606, 2006

3 Dahlin AM, "The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status" (16) : 1845-1855, 2010

4 Yang J, "Prognostic significance of gelsolin expression level and variability in non-small cell lung cancer" (46) : 29-42, 2004

5 Klampfer L, "Oncogenic Ras promotes butyrate-induced apoptosis through inhibition of gelsolin expression" (279) : 36680-36688, 2004

6 Dong Y, "Molecular mechanism of transcriptional repression of gelsolin in human breast cancer cells" (276) : 328-336, 2002

7 Noske A, "Loss of gelsolin expression in human ovarian carcinomas" (41) : 461-469, 2005

8 Herman JG, "Gene silencing in cancer in association with promoter hypermethylation" (349) : 2042-2054, 2003

9 Kim CS, "Gelsolin: a novel thyroid hormone receptor-beta interacting protein that modulates tumor progression in a mouse model of follicular thyroid cancer" (148) : 1306-1312, 2007

10 Tanaka M, "Gelsolin: a candidate for suppressor of human bladder cancer" (55) : 3228-3232, 1995

11 Litwin M, "Gelsolin in human colon adenocarcinoma cells with different metastatic potential" (56) : 739-743, 2009

12 Gremm D, "Gelsolin as a calcium-regulated actin filament-capping protein" (267) : 4339-4345, 2000

13 Dosaka-Akita H, "Frequent loss of gelsolin expression in non-small cell lung cancers of heavy smokers" (58) : 322-327, 1998

14 Mielnicki LM, "Epigenetic regulation of gelsolin expression in human breast cancer cells" (249) : 161-176, 1999

15 Winston JS, "Downregulation of gelsolin correlates with the progression to breast carcinoma" 65 : 11-21, 2001

16 Kim JH, "Downregulation of gelsolin and retinoic acid receptor beta expression in gastric cancer tissues through histone deacetylase 1" (19) : 218-224, 2004

17 Lee HK, "Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate" (40) : 14-19, 1999

18 Esteller M, "CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future" (21) : 5427-5440, 2002

19 Jones PA, "Cancer epigenetics comes of age" (21) : 163-167, 1999