TY - JOUR
T1 - A proteomic study of human merkel cell carcinoma
AU - Shao, Qiang
AU - Byrum, Stephanie D.
AU - Moreland, Linley E.
AU - Mackintosh, Samuel G.
AU - Kannan, Aarthi
AU - Lin, Zhenyu
AU - Morgan, Michael
AU - Stack, Brendan C.
AU - Cornelius, Lynn A.
AU - Tackett, Alan J.
AU - Gao, Ling
N1 - Funding Information:
Clarkson would like to thank Alberta Innovates Technology Futures, Encana and Shell for supporting his Chair in Unconventional Gas and Light Oil Research, Department of Geoscience, University of Calgary. All authors would like to thank the sponsors of Tight Oil Consortium ( www.tightoilconsortium.com ) for their ongoing support of our research. Finally, partial support for this research has been provided through an NSERC Discovery Grant to Clarkson.
PY - 2013
Y1 - 2013
N2 - Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular evens of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/ mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies.
AB - Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular evens of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/ mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies.
KW - Liquid tissue platform
KW - Merkel cell carcinoma
KW - PI3K/mTOR pathway
UR - http://www.scopus.com/inward/record.url?scp=84891369519&partnerID=8YFLogxK
U2 - 10.4172/jpb.1000291
DO - 10.4172/jpb.1000291
M3 - Article
C2 - 25284964
AN - SCOPUS:84891369519
SN - 0974-276X
VL - 6
SP - 275
EP - 282
JO - Journal of Proteomics and Bioinformatics
JF - Journal of Proteomics and Bioinformatics
IS - 11
ER -