کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525223 1546667 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleEpigenetic effects of inhibition of heat shock protein 90 (HSP90) in human pancreatic and colon cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleEpigenetic effects of inhibition of heat shock protein 90 (HSP90) in human pancreatic and colon cancer
چکیده انگلیسی


- DNA methylation involved in progression of pancreatic and colon cancer through silencing of key genes.
- Inhibition of HSP90 inhibited the growth of pancreatic and colorectal cancer cell lines with high baseline DNMT1 expression.
- Inhibition of HSP90 leads to downregulation of DNMT1, DNMT3a, DNMT3b and decrease in the frequency of DNA methylation.
- HSP90 inhibition induced expression of silenced p16, SPARC, and MLH-1 genes.

Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines. This in turn was associated with a drop in the fraction of methylated cytosine residues and re-expression of silenced genes including MLH-1, P16 and SPARC. These effects were validated in HT-29 tumors implanted subcutaneously in mice following in vivo administration of ganetespib. This work demonstrates the effectiveness of ganetespib, an HSP90 inhibitor in modulating DNA methylation through downregulation of DNMT expression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 402, 28 August 2017, Pages 110-116
نویسندگان
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