Characterization of the Breast Cancer Resistance Protein (BCRP/ABCG2) in clear cell renal cell carcinoma.

08:00 EDT 2nd August 2018 | BioPortfolio

Summary of "Characterization of the Breast Cancer Resistance Protein (BCRP/ABCG2) in clear cell renal cell carcinoma."

The efflux transporter breast cancer resistance protein BCRP/ABCG2 is well-known for its contribution to multi-drug resistance in cancer. Its relevance in cancer biology independent from drug efflux remains largely elusive. This study aimed at elucidating the biological relevance and regulatory mechanisms of BCRP/ABCG2 in clear cell renal cell carcinoma (ccRCC) and disease progression. Two independent ccRCC-cohorts (cohort-1 (KIRC/TCGA): n=453, cohort-2: n=64) were investigated to elucidate BCRP/ABCG2 mRNA and protein expression and their association with survival. The impact of BCRP/ABCG2 on response to sunitinib treatment was investigated in two independent sunitinib-treated ccRCC-cohorts based on mRNA levels. Moreover, underlying regulatory mechanisms for interindividual variability of BCRP/ABCG2 expression were systematically assessed. Owing to redundant functional properties, mRNA and protein expression of the multidrug resistance protein MDR1/ABCB1 were additionally evaluated in these cohorts. In independent ccRCC-cohorts, low BCRP/ABCG2 and MDR1/ABCB1 mRNA and protein expression were associated with severity (e.g. tumor stage) of ccRCC and poor cancer-specific survival. BCRP/ABCG2 and MDR1/ABCB1 mRNA expression were linked to decreased progression-free survival following sunitinib treatment. Germline and somatic variants influenced interindividual variability of BCRP/ABCG2 expression only moderately. miR-212-3p and miR-132-3p were identified to regulate BCRP/ABCG2 posttranscriptionally by interaction with the ABCG2 3'UTR as confirmed through reporter gene assays in RCC cell lines. In summary, BCRP/ABCG2 expression in ccRCC underlies considerable interindividual variability with impact on patient survival and response to sunitinib treatment. While germline or somatic genetic variants and DNA methylation cannot explain aberrant BCRP/ABCG2 expression, miR-212-3p and miR-132-3p were identified to contribute to posttranscriptional regulation of BCRP/ABCG2. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: International journal of cancer
ISSN: 1097-0215


DeepDyve research library

PubMed Articles [32385 Associated PubMed Articles listed on BioPortfolio]

Neoadjuvant Endocrine Therapy in Breast Cancer Upregulates the Cytotoxic Drug Pump ABCG2/BCRP, and May Lead to Resistance to Subsequent Chemotherapy.

Neoadjuvant treatments for primary breast cancer are becoming more common; however, little is known about how these impact on response to subsequent adjuvant therapies. Conveniently, neoadjuvant thera...

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression.

In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast can...

ABCG2 c.421C>A polymorphism alters nifedipine transport to breast milk in hypertensive breastfeeding women.

Nifedipine, a known substrate to breast cancer resistance protein (ABCG2/BCRP), is used for the treatment of hypertension during breastfeeding. This study aimed to evaluate the effect of ABCG2 c.421C...

Astragali radix and its main bioactive compounds activate the Nrf2-mediated signaling pathway to induce P-glycoprotein and breast cancer resistance protein.

Astragali radix (Huang Qi, HQ), a well-known Chinese herbal medicine, is widely coadministered with many other drugs for treating diseases. The potential herb-drug interactions (HDIs) possibly occur d...

TGF-β1 elevates P-gp and BCRP in hepatocellular carcinoma through HOTAIR/miR-145 axis.

Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor-β1 (TGF-β1) and overexpression of drug efflux transporters P-glycoprotein (P-gp) and breast cancer ...

Clinical Trials [17954 Associated Clinical Trials listed on BioPortfolio]

Genetic Polymorphisms of ABCG2/BCRP on the Transport of Nifedipine to Breast Milk.

This study aims to investigate the influence of the c.421C>A genetic polymorphism of the ABCG2 / BCRP transporter in the concentration ratio of nifedipine in maternal milk:plasma in hypert...

Expression of BCRP in Icteric Patients

The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Bile acids are also substrates of the drug efflux transporter b...

Role of Gene Variation in Effectiveness of Gleevec Treatment

This study will examine DNA from cancer patients previously treated with Gleevec to look for a variation (mutation) of the ABCG2 gene that may render the drug less effective in certain pat...

Study to Evaluate Effect of Lapatinib on Pharmacokinetics of JTZ-951 in Subjects With End-stage Renal Disease

Study to evaluate the effect of lapatinib, a breast cancer resistance protein (BCRP) inhibitor, on the pharmacokinetics (PK) of JTZ-951 and to evaluate the safety and tolerability of JTZ-9...

Unraveling KAdcyla Resistance In Human Epidermal Growth Factor Receptor 2(HER2) Positive Advanced Breast Cancer (KATIA)

The study aim is to perform a comprehensive and integrated characterization of mechanisms of primary and acquired resistance to Kadcyla in a prospective cohort of progressive/recurrent HER...

Medical and Biotech [MESH] Definitions

Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).

Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.

The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)

A secretoglobin that is produced by the MAMMARY GLAND of HUMANS and may be involved in the binding of ANDROGENS and other STEROIDS. The expression of this protein in normal breast epithelium and in human breast cancer has made it an important histological marker.

A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)

Quick Search


DeepDyve research library

Relevant Topics

Women's Health
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article