About: Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death
Creator	Jan, Rifat Lewis-Wambi, Joan Lui, Asona Ogony, Joshua Choi, Hye Sims, Peter
Source	Medline; PMC
abstract	INTRODUCTION: Estrogen deprivation using aromatase inhibitors (AIs) is currently the standard of care for postmenopausal women with hormone receptor-positive breast cancer. Unfortunately, the majority of patients treated with AIs eventually develop resistance, inevitably resulting in patient relapse and, ultimately, death. The mechanism by which resistance occurs is still not completely known, however, recent studies suggest that impaired/defective interferon signaling might play a role. In the present study, we assessed the functional role of IFITM1 and PLSCR1; two well-known interferon response genes in AI resistance. METHODS: Real-time PCR and Western blot analyses were used to assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI-resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells. Immunohistochemistry (IHC) staining was performed on tissue microarrays consisting of normal breast tissues, primary breast tumors, and AI-resistant recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate intracellular IFNα level. Neutralizing antibody was used to block type 1 interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFNα expression. RESULTS: We found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of IFITM1 significantly inhibited the ability of the resistant cells to proliferate, migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly increased expression of p21, Bax, and Noxa in these cells. Significantly elevated level of IFNα was detected in AI-resistant MCF-7:5C cells compared to parental MCF-7 cells and suppression of IFNα dramatically reduced IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly, neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells, thus confirming the involvement of the canonical IFNα signaling pathway in driving the overexpression of IFITM1 and other interferon-stimulated genes (ISGs) in the resistant cells. CONCLUSION: Overall, these results demonstrate that constitutive overexpression of ISGs enhances the progression of AI-resistant breast cancer and that suppression of IFITM1 and other ISGs sensitizes AI-resistant cells to estrogen-induced cell death. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0506-7) contains supplementary material, which is available to authorized users.
has issue date	2015-01-15(xsd:dateTime)
bibo:doi	10.1186/s13058-014-0506-7
bibo:pmid	25588716
has license	cc-by
sha1sum (hex)	0ce0b8bb68417974932e98c094ec93fbefc5193b
schema:url	https://doi.org/10.1186/s13058-014-0506-7
resource representing a document's title	Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death
has PubMed Central identifier	PMC4336497
has PubMed identifier	25588716
schema:publication	Breast Cancer Res
resource representing a document's body	covid:0ce0b8bb68417974932e98c094ec93fbefc5193b#body_text
is schema:about of	named entity 'GENES' named entity 'aromatase' named entity 'T47D' named entity 'interferon' named entity 'genes' named entity 'intracellular' named entity 'patient' named entity 'MCF-7' named entity 'The mechanism' named entity 'knockdown' named entity 'Targeting' named entity 'USING' named entity 'STAINING' named entity 'TISSUE MICROARRAYS' named entity 'TYPE 1' named entity 'ASSESS' named entity 'IRF-7' named entity 'MAJORITY' named entity 'PATIENT' named entity 'EXPRESSION' named entity 'BREAST CANCER CELLS' named entity 'STAT1' named entity 'IFNAR1' named entity 'RESISTANCE' named entity 'POSITIVE' named entity 'IFN' named entity 'RESISTANT' named entity 'STUDIES' named entity 'BREAST TUMORS' named entity 'ROLE' named entity 'PERFORMED' named entity 'FUNCTIONAL ROLE' named entity 'REAL-TIME PCR ' named entity 'ASSESSED' named entity 'HORMONE RECEPTOR' named entity 'TREATED WITH' named entity 'RELAPSE' named entity 'MECHANISM' named entity 'SUGGEST' named entity 'DEPRIVATION' named entity 'KNOWN' named entity 'COMPLETELY' named entity 'ENZYME-LINKED IMMUNOSORBENT ASSAY' named entity 'AIS' named entity 'WESTERN BLOT ANALYSES' named entity 'SIGNALING' named entity 'INTRACELLULAR' named entity 'PLAY' named entity 'IMMUNOHISTOCHEMISTRY' named entity 'GENES' named entity 'POSTMENOPAUSAL WOMEN' named entity 'MRNA' named entity 'INTRODUCTION' named entity 'INTERFERENCE RNA' named entity 'TUMORS' named entity 'INTERFERON ' named entity 'RESPONSE' named entity 'INDUCED' named entity 'TARGETING' named entity 'AROMATASE INHIBITOR' named entity 'STAT2' named entity 'IFITM1' named entity 'USED' named entity 'RECURRENCE' named entity 'ESTROGEN' named entity 'NEUTRALIZING ANTIBODY' named entity 'STUDY' named entity 'PRESENT' named entity 'T47D' named entity 'PROTEIN LEVELS' named entity 'SENSITIVE' named entity 'PATIENTS' named entity 'BLOCK' named entity 'STANDARD OF CARE' named entity 'BREAST TISSUES' named entity 'RESULTING IN'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software