title: TGF-β1 induces HMGA1 expression in human breast cancer cells: implications of the involvement of HMGA1 in TGF-β signaling.
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.
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tan
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ding
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Gebo
authors.initials: G
authors.lastname: Wen
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Renxian
authors.initials: R
authors.lastname: Cao
authors.affiliation: Guangdong Provincial Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D024003:HMGA Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D047368:Tumor Burden
chemical_list: D024003:HMGA Proteins; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt