NDLI: Activity of a Py-Im Polyamide Targeted to the Estrogen Response Element

Content Provider	PubMed Central
Author	Nickols, Nicholas G. Szablowski, Jerzy O. Hargrove, Amanda E. Li, Benjamin C. Raskatov, Jevgenij A. Dervan, Peter B.
Abstract	Pyrrole-imidazole (Py-Im) polyamides are a class of programmable DNA minor groove binders capable of modulating the activity of DNA-binding proteins and affecting changes in gene expression. Estrogen Receptor Alpha (ERα) is a ligand-activated hormone receptor that binds as a homodimer to estrogen response elements (EREs) and is a driving oncogene in a majority of breast cancers. We tested a selection of structurally similar Py-Im polyamides with differing DNA sequence specificity for activity against 17β-estadiol (E2) induced transcription and cytotoxicity in ERα positive, E2 stimulated T47D-KBLUC cells, which express luciferase under ERα control. The most active polyamide targeted the sequence: 5’-WGGWCW-3’ (W = A or T), which is the canonical ERE-half site. Whole transcriptome analysis using RNA-Seq revealed that treatment of E2-stimulated breast cancer cells with this polyamide reduced the effects of E2 on the majority of those most strongly affected by E2, but had much less effect on the majority of E2 induced transcripts. In vivo, this polyamide circulated at detectable levels following subcutaneous injection and reduced levels of ER-driven luciferase expression in xenografted tumors in mice after subcutaneous compound administration without significant host toxicity.
Related Links	http://dx.doi.org/10.1158/1535-7163.mct-12-1040
Ending Page	684
Page Count	10
Starting Page	675
File Format	PDF
ISSN	15357163
e-ISSN	15388514
Journal	Molecular cancer therapeutics
Issue Number	5
Volume Number	12
Language	English
Publisher Date	2013-05-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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