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

  • Authors:
    • Sun Young Yoon
    • Ha Reum Lee
    • Yoorim Park
    • Joo Heon Kim
    • Soo Young Kim
    • Suk Ran Yoon
    • Wang Jae Lee
    • Byung Joo Cho
    • Hyeyoung Min
    • Jung-Wook Bang
    • Hyunjeong Park
    • Sa Ik Bang
    • Daeho Cho
  • View Affiliations

  • Published online on: January 1, 2011     https://doi.org/10.3892/or_00001037
  • Pages: 23-31
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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-α with Tβ4 and the intracellular functional roles of Tβ4 on HIF-α activation. We examined HIF-1α, HIF-2α and Tβ4 expressions in clinical human breast carcinoma (n=70) by immunohistochemistry. We show that high expression of HIF-1α and HIF-2α 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 down-regulated, 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.

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January 2011
Volume 25 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yoon SY, Lee HR, Park Y, Kim JH, Kim SY, Yoon SR, Lee WJ, Cho BJ, Min H, Bang J, Bang J, et al: Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer . Oncol Rep 25: 23-31, 2011.
APA
Yoon, S.Y., Lee, H.R., Park, Y., Kim, J.H., Kim, S.Y., Yoon, S.R. ... Cho, D. (2011). Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer . Oncology Reports, 25, 23-31. https://doi.org/10.3892/or_00001037
MLA
Yoon, S. Y., Lee, H. R., Park, Y., Kim, J. H., Kim, S. Y., Yoon, S. R., Lee, W. J., Cho, B. J., Min, H., Bang, J., Park, H., Bang, S. I., Cho, D."Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer ". Oncology Reports 25.1 (2011): 23-31.
Chicago
Yoon, S. Y., Lee, H. R., Park, Y., Kim, J. H., Kim, S. Y., Yoon, S. R., Lee, W. J., Cho, B. J., Min, H., Bang, J., Park, H., Bang, S. I., Cho, D."Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer ". Oncology Reports 25, no. 1 (2011): 23-31. https://doi.org/10.3892/or_00001037