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Title 

Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer

Authors 

S Y YoonH R LeeY ParkJ H KimS Y KimSuk Ran YoonW J LeeB J ChoH MinJ W BangH ParkS I BangD Cho

Publisher 

Spandidos Publications

Issue Date 

2011

Citation 

Oncology Reports, vol. 25, no. 1, pp. 23-31

Keywords 

Breast carcinomaHIF-αLymph node metastasisThymosin β4VEGF-A

Abstract 

Intratumoral hypoxia has been correlated with distant metastatic potential. Two hypoxia inducible factors (HIFs), HIF-1α and HIF-2α are induced by hypoxia, and high expression of these proteins has been correlated to angiogenesis and distant metastasis. Thymosin β4 (Tβ4) is frequently highly expressed in cancer, and this overexpression correlates with malignant progression. The objective of this study was to investigate the clinical correlation of HIF-with Tβ4 and the intracellular functional roles of Tβ4 on HIF-α activation. We examined HIF-1α HIF-2 and Tβ4 expressions in clinical human breast carcinoma (n=70) by immunohistochemistry. We show that high expression of HIF-1-α and HIF-2-α strongly correlates with Tβ4 expression (P≤0.0001) and overexpression of Tβ4 correlates significantly with patients with lymph node metastasis (P<0.05) of human breast cancer. Additionally, we demonstrate that hypoxia up-regulates intracellular Tβ4 protein, which then affects HIF-α activity, which is the key in regulating VEGF expression. We confirmed that hypoxia-induced intracellular Tβ4 and HIF-α activities were reduced by interference of Tβ4 expression using Tβ4 shRNA lentivirus. Vascular epidermal growth factor (VEGF)-A, a well-recognized lymphangiogenic cytokine, was also downregulated, but VEGF-C and VEGF-D expressions were not affected. These findings suggest that the overexpression of Tβ4 is strongly associated with HIF-1α and HIF-2α expression and is also clinicopathologically involved with lymph node metastatic potential of breast cancer through the modulation of HIF-αactivation and induction of VEGF-A. Ultimately, these results highlight Tβ4 as a potentially therapeutic target in malignant cancers.

ISSN 

1021-335X

Link 

http://dx.doi.org/10.3892/or-00001037

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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