start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=1 article-no= start-page=22 end-page=28 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=200507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of histone deacetylase inhibitor FR901228 on expression level of telomerase reverse transcriptase in oral cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells. Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation. en-copyright= kn-copyright= en-aut-name=MurakamiJun en-aut-sei=Murakami en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaumiJun-ichi en-aut-sei=Asaumi en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiNoriko en-aut-sei=Kawai en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueTetsuyoshi en-aut-sei=Inoue en-aut-mei=Tetsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KokeguchiSusumu en-aut-sei=Kokeguchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiShoji en-aut-sei=Kawasaki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaNoriaki en-aut-sei=Tanaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubaraNagahide en-aut-sei=Matsubara en-aut-mei=Nagahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishiKanji en-aut-sei=Kishi en-aut-mei=Kanji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=2 en-affil= kn-affil=Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=3 en-affil= kn-affil=Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=4 en-affil= kn-affil=Department of Oral Pathology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=5 en-affil= kn-affil=Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=6 en-affil= kn-affil=Department of Oral Pathology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=7 en-affil= kn-affil=Department of Oral Microbiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=8 en-affil= kn-affil=Department of Oral Microbiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=9 en-affil= kn-affil=Department of Radiological Technology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=10 en-affil= kn-affil=Department of Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=11 en-affil= kn-affil=Department of Surgical Oncology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=12 en-affil= kn-affil=Department of Surgical Oncology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools affil-num=13 en-affil= kn-affil=Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools en-keyword=hTERT kn-keyword=hTERT en-keyword=FR901228 kn-keyword=FR901228 en-keyword=oral cancer kn-keyword=oral cancer en-keyword=HDAC inhibitor kn-keyword=HDAC inhibitor END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=597 end-page=603 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20042 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of demethylating agent 5-aza-2 '-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2'-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell tines. The expression levels of maspin mRNA were divided into two groups, which was the maspin tow-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell tines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.

en-copyright= kn-copyright= en-aut-name=MurakamiJun en-aut-sei=Murakami en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaumiJun-ichi en-aut-sei=Asaumi en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MakiYuu en-aut-sei=Maki en-aut-mei=Yuu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaiNoriyuki en-aut-sei=Nagai en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueTetsuyoshi en-aut-sei=Inoue en-aut-mei=Tetsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiShoji en-aut-sei=Kawasaki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaNoriaki en-aut-sei=Tanaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsubaraNagahide en-aut-sei=Matsubara en-aut-mei=Nagahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KishiKanji en-aut-sei=Kishi en-aut-mei=Kanji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University affil-num=8 en-affil= kn-affil=Okayama University affil-num=9 en-affil= kn-affil=Okayama University affil-num=10 en-affil= kn-affil=Okayama University affil-num=11 en-affil= kn-affil=Okayama University affil-num=12 en-affil= kn-affil=Okayama University en-keyword=maspin kn-keyword=maspin en-keyword=methylation kn-keyword=methylation en-keyword=5-aza-2 '-deoxycytidine kn-keyword=5-aza-2 '-deoxycytidine en-keyword=FR901228 kn-keyword=FR901228 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=1990 dt-pub=19900328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Actinobacillus actinomycetemcomitans の付着に関わる細胞表層成分に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=井上哲圭 kn-aut-sei=井上 kn-aut-mei=哲圭 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END