Asset Details
Do you wish to reserve the book?
MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways
Do you wish to request the book?
MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways
2011
Overview
Fulvestrant is a selective estrogen receptor downregulator (SERD) and highly effective antagonist to hormone-sensitive breast cancers following failure of previous tamoxifen or aromatase inhibitor therapies. However, after prolonged fulvestrant therapy, acquired resistance eventually occurs in the majority of breast cancer patients, due to poorly understood mechanisms. To examine a possible role(s) of aberrantly expressed microRNAs (miRNAs) in acquired fulvestrant resistance, we compared antiestrogen-resistant and -sensitive breast cancer cells, revealing the overexpression of miR-221/222 in the SERD-resistant cell lines. Fulvestrant treatment of estradiol (E2)- and fulvestrant-sensitive MCF7 cells resulted in increased expression of endogenous miR-221/222. Ectopic upregulation of miR-221/222 in estrogen receptor-α (ERα)-positive cell lines counteracted the effects of E2 depletion or fulvestrant-induced cell death, thus also conferring hormone-independent growth and fulvestrant resistance. In cells with acquired resistance to fulvestrant, miR-221/222 expression was essential for cell growth and cell cycle progression. To identify possible miR-221/222 targets, miR-221- or miR-222- induced alterations in global gene expression profiles and target gene expression at distinct time points were determined, revealing that miR-221/222 overexpression resulted in deregulation of multiple oncogenic signaling pathways previously associated with drug resistance. Activation of β-catenin by miR-221/222 contributed to estrogen-independent growth and fulvestrant resistance, whereas TGF-β-mediated growth inhibition was repressed by the two miRNAs. This first in-depth investigation into the role of miR-221/222 in acquired fulvestrant resistance, a clinically important problem, demonstrates that these two ‘oncomirs’ may represent promising therapeutic targets for treating hormone-independent, SERD-resistant breast cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Antineoplastic Agents - pharmacology
/ Biological and medical sciences
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - metabolism
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Estradiol - analogs & derivatives
/ Estrogen Antagonists - pharmacology
/ Estrogen Receptor alpha - metabolism
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Neoplastic - drug effects
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Medicine
/ MicroRNA
/ miRNA
/ Molecular and cellular biology
/ Oligonucleotide Array Sequence Analysis
/ Oncology
/ Proteins
/ RNA
/ Selective Estrogen Receptor Modulators - pharmacology
/ Signal Transduction - drug effects
/ Signal Transduction - genetics
/ Transforming Growth Factor beta - metabolism
/ Tumors
