Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis.
Differentially expressed nucleolar transforming growth factor-beta1 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-beta1 (TGF-beta1) in normal and malignant tissue and ectopic expression or treatment with TGF-beta1 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.
Kandalaft
Lana E
LE
Cell and Cancer Biology Branch, National Cancer Institute, Advanced Technology Center, Gaithersburg, MD 20877, USA. kandalal@mail.nih.gov
Zudaire
Enrique
E
Portal-Núñez
Sergio
S
Cuttitta
Frank
F
Jakowlew
Sonia B
SB
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C432963:TSPYL2 protein, human; D053773:Transforming Growth Factor beta1