Higher expression of the heterogeneous nuclear ribonucleoprotein k in melanoma.
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.


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.
Wen
Fushi
F
Department of Surgery, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Shen
Alex
A
Shanas
Reneé
R
Bhattacharyya
Achyut
A
Lian
Fangru
F
Hostetter
Galen
G
Shi
Jiaqi
J
D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism / Q000473:pathology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D039561:Eukaryotic Initiation Factor-4E; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases