TGF-β1 Induces HMGA1 Expression in Human Breast Cancer Cells: Implications of the Involvement of HMGA1 in TGF-β Signaling

Overview

Journal Int J Mol Med

Specialty Genetics

Date 2015 Jan 10

PMID 25572132

Citations 8

Authors

Xuyu Zu

Jing Zhong

Jingjing Tan

Li Tan

Dong Yang

Qinghai Zhang

Wenjun Ding

Wen Liu

Gebo Wen

Jianghua Liu

Renxian Cao

Yuyang Jiang

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression.

Citing Articles

HMGA1 Regulates the Expression of Replication-Dependent Histone Genes and Cell-Cycle in Breast Cancer Cells.

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High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential.

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