Format

Send to

Choose Destination
J Cell Mol Med. 2015 Oct;19(10):2385-96. doi: 10.1111/jcmm.12620. Epub 2015 Jul 27.

Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma.

Author information

1
Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
3
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
4
Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA, USA.
5
Division of Diagnostic Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

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.

KEYWORDS:

Cul4A; Gli1; hedgehog signalling; mTOR; malignant pleural mesothelioma

PMID:
26218750
PMCID:
PMC4594680
DOI:
10.1111/jcmm.12620
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center