Carcinogenesis Advance Access originally published online on April 1, 2008
Carcinogenesis 2008 29(6):1282-1289; doi:10.1093/carcin/bgn087
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Differentially expressed nucleolar transforming growth factor-β1 target (DENTT) exhibits an inhibitory role on tumorigenesis
Cell and Cancer Biology Branch
1 National Cancer Institute Angiogenesis Core Facility, National Cancer Institute, Advanced Technology Center, Gaithersburg, MD 20877, USA
2 Cell and Cancer Biology Branch, National Cancer Institute, Rockville, MD 20850, USA
* To whom correspondence should be addressed. Tel: +1 301 443 4492; Fax: +1 301 435 8036; Email: kandalal{at}mail.nih.gov
Differentially expressed nucleolar transforming growth factor-β1 target (DENTT), also known as testis-specific protein Y-encoded-like (TSPYL-2) and cell division autoantigen-1, is a member of the testis-specific protein Y-encoded (TSPY)/TSPY-L/SET/nucleosome assembly protein-1 superfamily. DENTT is expressed in various tissues including normal human lung. Here, we investigate the involvement of DENTT in cancer promotion and progression. DENTT messenger RNA (mRNA) and protein levels were shown to be markedly downregulated in human and mouse primary tumors and in human tumor cell lines. Overexpression of DENTT in human lung (A549-DENTT) and breast (MCF-7-DENTT) cancer cells resulted in diminished growth potential in anchorage-dependent growth assays and reduced capacity to form colonies under anchorage-independent culture conditions. The migratory potential of A549-DENTT and MCF-7-DENTT cells was reduced when compared with empty vector control cells. Treating human lung cell lines with demethylating agents increased DENTT expression significantly. DENTT expression pattern paralleled that of transforming growth factor-β1 (TGF-β1) in normal and malignant tissue and ectopic expression or treatment with TGF-β1 in lung cancer cells was followed by increased DENTT mRNA and protein levels. Collectively, our results suggest a role for DENTT as a suppressor of the tumorigenic phenotype.
Abbreviations: DENTT, differentially expressed nucleolar transforming growth factor-β1 target; EV, empty vector; FBS, fetal bovine serum; HT, heterozygous; LA, latent activatable; mRNA, messenger RNA; NAP-1, nucleosome assembly protein-1; RT-Q-PCR, real-time quantitative polymerase chain reaction; TGF-β1, transforming growth factor-β1; TSPY, testis-specific protein Y-encoded; TSPY-L, testis-specific protein Y-encoded-like
These authors contributed equally to this work. Received September 17, 2007; revised March 4, 2008; accepted March 24, 2008.