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A Proteomic Study of Human Merkel Cell Carcinoma

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 events of MCC carcinogenesis a...

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Autores principales: Shao, Qiang, Byrum, Stephanie D., Moreland, Linley E., Mackintosh, Samuel G., Kannan, Aarthi, Lin, Zhenyu, Morgan, Michael, Stack, Brendan C., Cornelius, Lynn A., Tackett, Alan J., Gao, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181674/
https://www.ncbi.nlm.nih.gov/pubmed/25284964
http://dx.doi.org/10.4172/jpb.1000291
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author Shao, Qiang
Byrum, Stephanie D.
Moreland, Linley E.
Mackintosh, Samuel G.
Kannan, Aarthi
Lin, Zhenyu
Morgan, Michael
Stack, Brendan C.
Cornelius, Lynn A.
Tackett, Alan J.
Gao, Ling
author_facet Shao, Qiang
Byrum, Stephanie D.
Moreland, Linley E.
Mackintosh, Samuel G.
Kannan, Aarthi
Lin, Zhenyu
Morgan, Michael
Stack, Brendan C.
Cornelius, Lynn A.
Tackett, Alan J.
Gao, Ling
author_sort Shao, Qiang
collection PubMed
description 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 events 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.
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spelling pubmed-41816742014-10-02 A Proteomic Study of Human Merkel Cell Carcinoma Shao, Qiang Byrum, Stephanie D. Moreland, Linley E. Mackintosh, Samuel G. Kannan, Aarthi Lin, Zhenyu Morgan, Michael Stack, Brendan C. Cornelius, Lynn A. Tackett, Alan J. Gao, Ling J Proteomics Bioinform Article 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 events 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. 2013-11-25 /pmc/articles/PMC4181674/ /pubmed/25284964 http://dx.doi.org/10.4172/jpb.1000291 Text en Copyright: © 2013 Shao Q, et al. http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Shao, Qiang
Byrum, Stephanie D.
Moreland, Linley E.
Mackintosh, Samuel G.
Kannan, Aarthi
Lin, Zhenyu
Morgan, Michael
Stack, Brendan C.
Cornelius, Lynn A.
Tackett, Alan J.
Gao, Ling
A Proteomic Study of Human Merkel Cell Carcinoma
title A Proteomic Study of Human Merkel Cell Carcinoma
title_full A Proteomic Study of Human Merkel Cell Carcinoma
title_fullStr A Proteomic Study of Human Merkel Cell Carcinoma
title_full_unstemmed A Proteomic Study of Human Merkel Cell Carcinoma
title_short A Proteomic Study of Human Merkel Cell Carcinoma
title_sort proteomic study of human merkel cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181674/
https://www.ncbi.nlm.nih.gov/pubmed/25284964
http://dx.doi.org/10.4172/jpb.1000291
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