Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer

Autor: Madeleine L. Craze, Brendah K. Masisi, Lutfi Alfarsi, Rokaya El-Ansari, Ian O. Ellis, Emad A. Rakha, Omar J. Mohammed, Andrew R. Green
Rok vydání: 2020
Předmět:
0301 basic medicine
SLC3A2
Drug resistance
Kaplan-Meier Estimate
medicine.disease_cause
SLC7A5
lcsh:Chemistry
Cohort Studies
0302 clinical medicine
Neoplasm Metastasis
RNA
Small Interfering
skin and connective tissue diseases
lcsh:QH301-705.5
Spectroscopy
Gene knockdown
General Medicine
Middle Aged
Prognosis
Computer Science Applications
oestrogen receptor
Gene Expression Regulation
Neoplastic
Receptors
Estrogen
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Regression Analysis
Female
psychological phenomena and processes
medicine.drug
Antineoplastic Agents
Hormonal
Fusion Regulatory Protein 1
Heavy Chain
Breast Neoplasms
Catalysis
Article
Large Neutral Amino Acid-Transporter 1
Inorganic Chemistry
endocrine resistance
03 medical and health sciences
Breast cancer
breast cancer
Cell Line
Tumor
mental disorders
medicine
Biomarkers
Tumor
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Messenger RNA
business.industry
Organic Chemistry
medicine.disease
In vitro
Tamoxifen
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Drug Resistance
Neoplasm
Cancer cell
Cancer research
business
Carcinogenesis
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 4
International Journal of Molecular Sciences, Vol 21, Iss 4, p 1407 (2020)
ISSN: 1422-0067
Popis: The majority of breast cancers are oestrogen-receptor-positive (ER+) and are subject to endocrine therapy
however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. The SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino-acid transporters lead to metabolic reprogramming, which contributes to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting responses to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2&minus
breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in a subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2&minus
breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapies.
Databáze: OpenAIRE
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