Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer.

Minhua Wu,Yuxin Zhou,Weizhu Wu,Limu Wen,Jinhua Ding,Zhenbo Xu

doi:10.1155/2021/6618519

Abstract

Objective The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer. Methods The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway to study the molecular mechanism of secondary endocrine resistance in Luminal breast cancer. Results The downregulation of MLF1IP could significantly increase the drug sensitivity of Michigan Cancer Foundation-7 (MCF-7) cells and also inhibit the proliferation of MCF-7 cells under the stimulation of drugs. Western blot results showed that the expression of Bcl-2-associated X (BAX), Caspase3, Caspase7, and Caspase9 proteins increased when MLF1IP was downregulated. The results of the PI3K/AKT signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression of MCF7-shRNA was higher than that of MCF7-NC cells, while the expression of p-AKT was lower than that of MCF7-NC cells. Conclusions (1) MLF1IP-related apoptosis resistance plays an essential role in MLF1IP-mediated secondary resistance of breast cancer cells. (2) MLF1IP promotes AKT phosphorylation by inhibiting the PTEN expression, thus activating the PI3K/AKT signaling pathway and causing the secondary resistance of Luminal breast cancer. (3) MLF1IP can be used as a factor to predict the endocrine resistance of Luminal breast cancer.

Highlights

According to statistics, nearly 1.7 million new breast cancer cases are diagnosed every year across the world, accounting for a quarter of malignant tumors in women
Polymerase Chain Reaction (PCR) was used to detect the relative expression level of myeloid leukemia factor 1-interacting proteins (MLF1IP) mRNA in Michigan Cancer Foundation-7 (MCF-7) cells treated with TAM to explore the role of MLF1IP in endocrine resistance of Luminal breast cancer
It revealed that the expression level of MLF1IP mRNA in MCF-7 cells was 42% higher than that in the control group treated with phosphate buffer solution (PBS) after 2 weeks of treatment with 16 μM TAM, and the difference was statistically significant

Summary

Introduction

Nearly 1.7 million new breast cancer cases are diagnosed every year across the world, accounting for a quarter of malignant tumors in women. More than half a million women worldwide die of breast cancer every year [1, 2]. Breast cancer has become one of the most common malignant tumors in modern women and severely affects women’s health and life [3]. With the development of molecular biology, the research goes deep into breast cancer. Different treatments are used in patients with different breast cancers. Endocrine therapy (ET), as the primary treatment to breast cancers, can effectively reduce the recurrence rate and mortality of breast cancer. Tamoxifen (TAM) is the main drug in endocrine therapy for Luminal breast cancer, but some patients have resistance to it.

Methods

Results

Discussion

Conclusion