Yeste-Velasco, Marc, Mao, Xueying, Grose, Richard, Kudahetti, Sakunthala C, Lin, Dongmei, Marzec, Jacek, Vasiljevic, Natasa, Chaplin, Tracy, Xue, Liyan, Xu, Maojia, Foster, Julie M, Karnam, Santi S, James, Sharon Y, Chioni, Athina-Myrto, Gould, David, Lorincz, Attila T, Oliver, R Tim D, Chelala, Claude, Thomas, Gareth M, Shipley, Janet M, Mather, Stephen J, Berney, Daniel M, Young, Bryan D and Lu, Yong-Jie (2014) Identification of ZDHHC14 as a novel human tumour suppressor gene. The Journal of Pathology, 232(5), pp. 566-577. ISSN (print) 0022-3417
Abstract
Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14. The expression of ZDHHC14, a putative protein palmitoyltransferase with unknown cellular function, was decreased at both RNA and protein levels in testicular germ cell tumours. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. In addition to our findings of genetic and protein expression changes in clinical samples, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspase-dependent apoptotic pathway and heterozygous knockout of ZDHHC14 decreased cell colony formation ability. Finally, we confirmed our in vitro findings of the tumour suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumourigenesis. Thus, we have identified a novel tumour suppressor gene that is commonly down-regulated in testicular germ cell tumours and prostate cancer, as well as given insight into the cellular functional role of ZDHHC14, a potential protein palmitoyltransferase that may play a key protective role in cancer.
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