miR-484 suppresses endocrine therapy-resistant cells by inhibiting KLF4-induced cancer stem cells in estrogen receptor-positive cancers

Autor: Hong Li, Quanxin Qu, Yulei Wei
Rok vydání: 2020
Předmět:
0301 basic medicine
Antineoplastic Agents
Hormonal
Kruppel-Like Transcription Factors
Estrogen receptor
Breast Neoplasms
Kruppel-Like Factor 4
Mice
03 medical and health sciences
0302 clinical medicine
Breast cancer
Gentamicin protection assay
SOX2
Cancer stem cell
Biomarkers
Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Pharmacology (medical)
Radiology
Nuclear Medicine and imaging
skin and connective tissue diseases
biology
business.industry
CD44
Estrogen Receptor alpha
General Medicine
medicine.disease
Xenograft Model Antitumor Assays
Gene Expression Regulation
Neoplastic
MicroRNAs
Tamoxifen
030104 developmental biology
Oncology
Drug Resistance
Neoplasm
KLF4
030220 oncology & carcinogenesis
MCF-7 Cells
Neoplastic Stem Cells
biology.protein
Cancer research
Female
business
medicine.drug
Zdroj: Breast Cancer. 28:175-186
ISSN: 1880-4233
1340-6868
DOI: 10.1007/s12282-020-01152-6
Popis: Endocrine therapy (mainly anti-estrogen therapy) is the mainstay of treatment for estrogen receptor (ER) positive breast cancer (BCa). However, approximately one-third of BCa patients who receive endocrine therapy may develop resistance. The detailed mechanism is still unclear. MCF7 and T-47D cells were treated with ERα antagonist tamoxifen for 2 months until they became tamoxifen-resistant. qPCR was used to detect the stem markers like CD44, OCT4 and SOX2. Flow cytometry and sphere formation were performed to test the stemness. Cell growth and invasiveness were measured by MTS assay, xenograft mouse model, and invasion assay. We found that tamoxifen resistant BCa cells acquired certain malignant phenotypes, such as higher expression of KLF4, stemness and enhanced invasiveness. Furthermore, miR-484 was found to act as a tumor suppressor and directly downregulated KLF4. KLF4-induced cancer stem cell (CSCs) contributes to anti-ER therapy resistant and is a potential target in endocrine therapy-resistant cancers.
Databáze: OpenAIRE
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