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Association of growth factors, HIF-1 and NF-κB expression with proteasomes in endometrial cancer

Abstract

Insulin-like growth factors (IGFs), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF-1), and nuclear factor kappa-B (NF-κB) are known to play an important role in endometrial cancer pathogenesis. However, the proteolytic regulation of these factors is still poorly understood. We studied the correlation between chymotrypsin-like activity of proteasomes and IGF-I, IGF-II, VEGF, HIF-1, and NF-κB levels in endometrial cancer tissues. It was shown that the total activity of proteasomes and the activity of the 20S and 26S proteasomes in malignant tumors were significantly higher than those observed in the normal endometrium. Negative relationships between the proteasome activity and IGF-I, HIF-1, and NF-κB p50 expressions were found. High 20S proteasome activity was associated with increase of HIF-1 level. Positive relationships between IGF-I expression and two classic forms of NF-κB p50 and p65 in endometrial cancer were revealed. The data obtained indicate the possible proteasomal regulation of growth and transcription factors. The major pool of IGF-I is located in the extracellular space, and it is likely that extracellular proteasomes also take part in the regulation of the IGF-I content. The present data show the evidence of proteasome regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.

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Abbreviations

20S and 26S:

Proteasome

IGF-I, IGF-II:

Insulin-like growth factors

IGFBPs:

Insulin growth factors binding proteins

IRS:

Insulin receptor substrate

HIF-1:

Hypoxia-inducible factor-1

NF-κB:

Nuclear factor kappa-B

VEGF:

Vascular endothelial growth factor

pVHL:

Von Hippel–Lindau protein

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Acknowledgments

This study was supported by the Federal target program “Scientific and scientific-pedagogical personnel of innovative Russia” in 2009–2013 (Governmental Contract No. P320).

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Correspondence to Ludmila V. Spirina.

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Spirina, L.V., Yunusova, N.V., Kondakova, I.V. et al. Association of growth factors, HIF-1 and NF-κB expression with proteasomes in endometrial cancer. Mol Biol Rep 39, 8655–8662 (2012). https://doi.org/10.1007/s11033-012-1720-y

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Keywords

  • Insulin-like growth factors
  • Vascular endothelial growth factor
  • Hypoxia-inducible factor-1
  • Proteasome
  • Nuclear factor kappa-B
  • Endometrial cancer