gstp1 dna methylation and expression status is indicative of 5-aza-2′-deoxycytidine efficacy in human prostate cancer cellsgstp1 dna甲基化和表达状态表明5-aza-2u2032脱氧胞苷在人类前列腺癌细胞的功效.pdfVIP

下载本文档

0
0
约7.86万字
约 11页
2017-09-01 发布于上海
举报
版权申诉

gstp1 dna methylation and expression status is indicative of 5-aza-2′-deoxycytidine efficacy in human prostate cancer cellsgstp1 dna甲基化和表达状态表明5-aza-2u2032脱氧胞苷在人类前列腺癌细胞的功效.pdf

1、有哪些信誉好的足球投注网站（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

gstp1 dna methylation and expression status is indicative of 5-aza-2′-deoxycytidine efficacy in human prostate cancer cellsgstp1 dna甲基化和表达状态表明5-aza-2u2032脱氧胞苷在人类前列腺癌细胞的功效

GSTP1 DNA Methylation and Expression Status Is Indicative of 5-aza-29-Deoxycytidine Efficacy in Human Prostate Cancer Cells ¤ Karen Chiam , Margaret M. Centenera, Lisa M. Butler, Wayne D. Tilley, Tina Bianco-Miotto* Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, University of Adelaide, Hanson Institute, Adelaide, Australia Abstract DNA methylation plays an important role in carcinogenesis and the reversibility of this epigenetic modification makes it a potential therapeutic target. To date, DNA methyltransferase inhibitors (DNMTi) have not demonstrated clinical efficacy in prostate cancer, with one of the major obstacles being the inability to monitor drug activity during the trial. Given the high frequency and specificity of GSTP1 DNA methylation in prostate cancer, we investigated whether GSTP1 is a useful marker of DNMTi treatment efficacy. LNCaP prostate cancer cells were treated with 5-aza-29-deoxycytidine (5-aza-CdR) either with a single high dose (5–20 mM), every alternate day (0.1–10 mM) or daily (0.005–2.5 mM). A daily treatment regimen with 5-aza- CdR was optimal, with significant suppression of cell proliferation achieved with doses of 0.05 mM or greater (p,0.0001) and induction of cell death from 0.5 mM (p,0.0001). In contrast, treatment with a single high dose of 20 mM 5-aza-CdR inhibited cell proliferation but was not able to induce cell death. Demethylation of GSTP1 was observed with doses of 5-aza-CdR that induced significant suppression of cell proliferation ($0.05 mM). Re-expression of the GSTP1 protein was observed only at doses of 5-aza-CdR ($0.5 mM) associated with induction of cell death. Treatment of LNCaP cells with a more stable DNMTi, Zebularine required at least a 100-fold higher dose ($50 mM) to inhibit proliferation and was less potent in inducing cell death, which corresponded to a lack of GSTP1