Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma. Issue 10 (27th July 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of cellular and molecular medicine. Volume 19:Issue 10(2015)
• Page Start: 2385
• Page End: 2396
• Publication Date: 2015-07-27
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12620
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12620-abs-0001"> <title>Abstract</title> <p>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 <italic>in vitro</italic> 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 <italic>Cul4A</italic> copy number identified by fluorescence <italic>in situ</italic> hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and <italic>Cul4A</italic> 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 (<italic>P</italic> &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.</p> </abstract>