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KMID : 1134120180210030259
Journal of Breast Cancer
2018 Volume.21 No. 3 p.259 ~ p.266
Hypoxia-Inducible Factor 1¥á Regulates the Transforming Growth Factor ¥â1/SMAD Family Member 3 Pathway to Promote Breast Cancer Progression
Peng Jianheng

Wang Xiaolin
Ran Liang
Song Junlong
Luo Rong
Wang Yonghong
Abstract
Purpose: The transforming growth factor ¥â1 (TGF-¥â1)/SMAD family member 3 (SMAD3) pathway, and hypoxia-inducible factor 1¥á (HIF-1¥á) are two key players in various types of malignancies including breast cancer. The TGF-¥â1/SMAD3 pathway can interact with HIF-1¥á in some diseases; however, their interaction in breast cancer is still unknown. Therefore, our study aimed to investigate the interactions between the TGF-¥â1/SMAD3 pathway and HIF-1¥á in breast cancer.

Methods: Expression of HIF-1¥á in serum of breast cancer patients and healthy controls was detected by quantitative reverse transcription polymerase chain reaction, and the diagnostic value of HIF-1¥á for breast cancer was evaluated by receiver operating characteristic curve analysis. Breast cancer cell lines overexpressing SMAD3 and HIF-1¥á were established. Cell apoptosis and proliferation following different treatments were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and cell counting kit-8, respectively. Expression of related proteins was detected by western blot.

Results: Serum levels of HIF-1¥á were higher in breast cancer patients than in normal controls. Both SMAD3 and HIF-1¥á overexpression inhibited cell apoptosis and promoted cell proliferation. Treatment with inhibitors of HIF-1¥á and SMAD3 promoted apoptosis in breast cancer cells and inhibited their proliferation. Overexpression of HIF-1¥á promoted the expression of TGF-¥â1 and SMAD3, while SMAD3 overexpression did not significantly affect expression of HIF-1¥á or TGF-¥â1.

Conclusion: HIF-1¥á serves as an upstream regulator of the TGF-¥â1/SMAD3 pathway and promotes the growth of breast cancer.
KEYWORD
Breast neoplasms, Hypoxia-inducible factor 1, Smad3 protein, Transforming growth factor beta1
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