Higher expression of the heterogeneous nuclear ribonucleoprotein k in melanoma

Ann Surg Oncol. 2010 Oct;17(10):2619-27. doi: 10.1245/s10434-010-1121-1. Epub 2010 May 25.

Abstract

Background: The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. Oncogenes c-Src, c-myc, and eIF4E are regulated by hnRNP K. We have shown an increased cytoplasmic hnRNP K in pancreatic cancer. In the present study, we investigated the altered expression of hnRNP K protein and its correlation with p-ERK in melanoma using human melanoma cell lines and tissue microarray.

Materials and methods: The protein levels of hnRNP K and p-ERK in 8 human melanoma cell lines and a melanoma progression tissue microarray containing 80 melanoma, 23 dysplastic nevi, and 14 benign nevi specimens were analyzed using Western blot and immunohistochemistry analysis. hnRNP K was knocked down by siRNA, and its effect on melanoma cells was assessed.

Results: We showed a higher hnRNP K protein level in both melanoma cell lines and melanoma tissue specimens, which correlated with a higher c-myc expression. An increase in the cytoplasmic hnRNP K and eIF4E protein levels in melanoma cells is also seen. p-ERK level was also higher in dysplastic nevi and melanoma tissues, but did not correlate with hnRNP K protein level. We then demonstrated that knocking down of hnRNP K by siRNA inhibited melanoma cell growth and colony formation, as well as c-myc expression.

Conclusions: hnRNP K expression correlated with melanoma and may play a role in melanoma tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cytoplasm / metabolism
  • Dysplastic Nevus Syndrome / metabolism
  • Dysplastic Nevus Syndrome / pathology
  • Eukaryotic Initiation Factor-4E / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein K / antagonists & inhibitors
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Phosphorylation
  • Prognosis
  • RNA, Small Interfering / pharmacology
  • Tissue Array Analysis
  • Tumor Cells, Cultured

Substances

  • Eukaryotic Initiation Factor-4E
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • RNA, Small Interfering
  • Extracellular Signal-Regulated MAP Kinases