title: Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma.
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.
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.|Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.|Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ping-Chih
authors.initials: PC
authors.lastname: Hsu
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hsieh
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Chan
authors.affiliation: Division of Diagnostic Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Au
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: You
mesh_terms: D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C114234:CUL4A protein, human; D044842:Cullin Proteins; C400551:GLI1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
keywords: Cul4A; Gli1; hedgehog signalling; mTOR; malignant pleural mesothelioma