Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer

Mohsen Taheri,Jamshid Motalebzadeh,Frouzandeh Mahjoubi

doi:10.31557/apjcp.2018.19.11.3111

Abstract

Background:Breast cancer is the most common malignancy in women. Multidrug resistance (MDR) is still a great obstacle of breast cancer chemotherapy. We have previously shown that multidrug resistance-associated protein 1 (MRP1) is associated with response to neoadjuvant chemotherapy. The lung resistance-related protein (LRP) is identified as a prognostic marker and response to treatment factor which has been studied mainly in hematological malignancy and leukemia. In this study, we aimed to analyze LRP expression and possible correlation between the expression level of this gene with MRP1 as a candidate marker for chemotherapy resistance.Materials and Methods:We collected 54 breast tumors and adjacent normal tissues from Iranian breast cancer patients and Real time RT-PCR was employed to measure the gene expression level in our samples.Results:MRP1 and LRP expression level were significantly lower in tumor tissues of the patients responding to chemotherapy compared to non-responding patients. No relation between the expression level of either of these genes and clinicopathology markers was found.Conclusion:Our results suggest that LRP gene expression is correlated to MRP1 in human breast cancer cells and may affect the clinical response to treatment.

Highlights

Breast cancer with an estimated 1.7 million cases and 521,900 deaths in 2012 is known as the most common malignancy in women
This study was done on 54 breast cancer patients to assess the expression levels of multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP) on clinicopathology criteria and response to treatment
Several proteins have been identified that are able to prevent the intracellular accumulation of anticancer agents by efflux mechanism such as MDR1 and MRP1 (Fojo and Coley, 2007)

Summary

Introduction

Breast cancer with an estimated 1.7 million cases and 521,900 deaths in 2012 is known as the most common malignancy in women. Breast cancer is considered as one of the most responsive to chemotherapy, but most of the tumors that initially response to drugs become resistance (Burger et al, 2003) and the incidence of resistance increases with breast cancer progression (Martin et al, 2014) This phenomenon is named as Multi Drug Resistance (MDR) in which cancer cells become resistant to the wide spectrum of drugs with different structure and function (Gottesman, 2002). Several mechanisms responsible for drug resistance have been identified including mutation in or overexpression of the drug’s target, drug inactivation and efflux of the drug from the cell by ATP Binding Cassette (ABC) transporters (Motalebzadeh et al, 2017). Conclusion: Our results suggest that LRP gene expression is correlated to MRP1 in human breast cancer cells and may affect the clinical response to treatment

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