Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma.

TitleCul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma.
Publication TypeJournal Article
Year of Publication2015
AuthorsYang Y-L, Ni J, Hsu P-C, Mao J-H, Hsieh D, Xu A, Chan G, Au A, Xu Z, Jablons DM, You L
JournalJ Cell Mol Med
Volume19
Issue10
Pagination2385-96
Date Published2015 Oct
ISSN1582-4934
KeywordsCase-Control Studies, Cell Line, Tumor, Chi-Square Distribution, Cullin Proteins, Gene Dosage, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Lung Neoplasms, Mesothelioma, Pleural Neoplasms, Real-Time Polymerase Chain Reaction, RNA, Messenger, Transcription Factors
Abstract

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 < 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.

DOI10.1111/jcmm.12620
Alternate JournalJ. Cell. Mol. Med.
PubMed ID26218750
PubMed Central IDPMC4594680
Grant ListR01 CA140654-01A1 / CA / NCI NIH HHS / United States