High glucose promotes breast cancer proliferation and metastasis by impairing angiotensinogen expression.

Shichao Sun,Lei Bai,Yao Sun,Xiaoping Rong

doi:10.1042/bsr20190436

Abstract

A number of investigations have addressed the importance of high glucose in breast cancer, however, the involvement of angiotensinogen (AGT) in this scenario is yet to be defined. Here we set out to analyze the potential pro-tumor effects of high glucose in breast cancer, and understand the underlying molecular mechanism. We demonstrated that high glucose promoted cell proliferation, viability, and anchorage-independent growth of breast cancer cells. In addition, the migrative and invasive capacities were significantly enhanced by high glucose medium. Mechanistically, AGT expression was inhibited by high glucose at both transcriptional and translational levels. High AGT remarkably suppressed proliferation, inhibited viability, and compromised migration/invasion of breast cancer cells. Most importantly, ectopic introduction of AGT almost completely abrogated pro-tumor effects of high glucose. Our study has characterized the pro-tumor properties of high glucose in breast cancer cells, which is predominantly attributed to the suppression of AGT.

Highlights

Breast cancer is one of the most common gynecological malignancies, which accounts for 25% of all incidences
We first set out to evaluate the potential influence of high glucose on proliferative index in breast cancer cells
Our data clearly showed that supplementation with 25 mM of glucose significantly promoted proliferation of both MCF-7 and MDA-MB-231 cells, in comparison with 5.5 mM glucose in the normal culture medium (Figure 1A,B), which implicated a critical role of high blood glucose in the tumor biology of breast cancer

Summary

Introduction

Breast cancer is one of the most common gynecological malignancies, which accounts for 25% of all incidences. Preventive therapies are sometimes applicable to those population with high risk to develop breast cancer, including medications such as tamoxifen and raloxifene and surgical removal of both breasts. Clinical managements of this disease depend on cancer type, extent of disease, and individual health conditions, as well as surgery, radiation therapy, chemotherapy, hormonal therapy, and targeted therapy [5]. Prognosis of this disease varies and overall 5-year survival rates are approximately 80–90% in the U.S.A

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Conclusion