Over expression of HIF1α is associated with inactivation of both LimD1 and VHL in renal cell carcinoma: Clinical importance

Pathol Res Pract. 2017 Dec;213(12):1477-1481. doi: 10.1016/j.prp.2017.10.009. Epub 2017 Oct 10.

Abstract

It is evident that the association of LimD1 and VHL could regulate stabilization of HIF1α protein. In this study, the expression of LimD1, VHL and HIF1α was analyzed in primary renal cell carcinoma (RCC) samples to understand their association with development of the disease. For this purpose, immunohistochemical expression analysis of LimD1, VHL and HIF1α was performed along with proliferation marker PCNA in 32 primary RCC samples in different subtypes at different clinical stages of Indian patients (year: 2014-2016). Significant decrease (P<0.05) in LimD1 and VHL expression was observed in different subtypes of RCC and in early invasive lesions. High nuclear expression of HIF1α was seen in different subtypes as well as in early invasive lesions. The LimD1 and VHL expression strongly correlated with each other, while inversely correlated with HIF1α. On the other hand, increased expression of PCNA was seen in different sub types and in early invasive lesions. The PCNA expression was negatively correlated with LimD1 and VHL expression and positively correlated with HIF1α. Thus, our data indicates that the reduced expression of LimD1 and VHL might have synergistic effect on induction of HIF1α resulting increased cellular proliferation and progression of the disease.

Keywords: HIF1α; LimD1; PCNA; Renal cell carcinoma; VHL.

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney Neoplasms / pathology
  • LIM Domain Proteins / metabolism*
  • Male
  • Middle Aged
  • Tumor Suppressor Proteins / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • LIMD1 protein, human
  • Tumor Suppressor Proteins
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human