Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in ...

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Veröffentlicht in:Journal of cellular and molecular medicine 2015-10, Vol.19 (10), p.2385-2396
Hauptverfasser: Yang, Yi‐Lin, Ni, Jian, Hsu, Ping‐Chih, Mao, Jian‐Hua, Hsieh, David, Xu, Angela, Chan, Geraldine, Au, Alfred, Xu, Zhidong, Jablons, David M., You, Liang
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container_title Journal of cellular and molecular medicine
container_volume 19
creator Yang, Yi‐Lin
Ni, Jian
Hsu, Ping‐Chih
Mao, Jian‐Hua
Hsieh, David
Xu, Angela
Chan, Geraldine
Au, Alfred
Xu, Zhidong
Jablons, David M.
You, Liang
description Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P 
doi_str_mv 10.1111/jcmm.12620
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Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P &lt; 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.12620</identifier><identifier>PMID: 26218750</identifier><language>eng</language><publisher>England: John Wiley &amp; Sons, Inc</publisher><subject>Artificial chromosomes ; BASIC BIOLOGICAL SCIENCES ; Case-Control Studies ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Chi-Square Distribution ; Copy number ; Cul4A ; Cullin Proteins - genetics ; Cullin Proteins - metabolism ; Fluorescence ; Fluorescence in situ hybridization ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Gli1 ; hedgehog signalling ; Humans ; Hybridization ; Hybridization analysis ; Immunohistochemistry ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; malignant pleural mesothelioma ; Medical prognosis ; Medical research ; Mesothelioma ; Mesothelioma - genetics ; Mesothelioma - metabolism ; Mesothelioma - pathology ; Mesothelioma, Malignant ; mTOR ; Original ; Pleural Neoplasms - metabolism ; Pleural Neoplasms - pathology ; Protein expression ; Proteins ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; siRNA ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumors ; Zinc Finger Protein GLI1</subject><ispartof>Journal of cellular and molecular medicine, 2015-10, Vol.19 (10), p.2385-2396</ispartof><rights>2015 The Authors. 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Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P &lt; 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. 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Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P &lt; 0.05, chi‐square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.</abstract><cop>England</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>26218750</pmid><doi>10.1111/jcmm.12620</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Artificial chromosomes
BASIC BIOLOGICAL SCIENCES
Case-Control Studies
Cell cycle
Cell growth
Cell Line, Tumor
Chi-Square Distribution
Copy number
Cul4A
Cullin Proteins - genetics
Cullin Proteins - metabolism
Fluorescence
Fluorescence in situ hybridization
Gene Dosage
Gene Expression Regulation, Neoplastic
Gli1
hedgehog signalling
Humans
Hybridization
Hybridization analysis
Immunohistochemistry
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
malignant pleural mesothelioma
Medical prognosis
Medical research
Mesothelioma
Mesothelioma - genetics
Mesothelioma - metabolism
Mesothelioma - pathology
Mesothelioma, Malignant
mTOR
Original
Pleural Neoplasms - metabolism
Pleural Neoplasms - pathology
Protein expression
Proteins
Real-Time Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
siRNA
Transcription Factors - genetics
Transcription Factors - metabolism
Tumors
Zinc Finger Protein GLI1
title Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma
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