title: Phylogenetic analysis, expression patterns, and transcriptional regulation of human CTEN gene.
abstract: Cten is a focal adhesion molecule and a member of the tensin family. Its expression is highly enriched in the prostate and placenta, suggesting that cten gene might be closely associated with mammalian species. Recent studies have reported that cten expression is frequently up-regulated in a variety of cancers and its levels appear to correlate with tumorigenicity. Here, we have (1) analyzed cten sequences of various species to build a phylogenetic tree, (2) examined cten mRNA levels in human and mouse tissues to establish its expression profiles, and (3) determined the promoter region of human CTEN gene in cell lines and in a mouse model to understand its transcriptional regulation. Our analyses indicate that all currently known cten genes are present in mammals. The prostate and placenta are the two most cten abundant tissues in human and mouse, meanwhile brain and lung also express low levels of cten. Results from cell culture reporter assays demonstrate that a 327-bp fragment is the shortest functional promoter. All functional promoter constructs produce 40- to 160-fold increases in luciferase reporter activities in normal prostate cells, whereas lower activities (<40-fold) are detected in non-prostatic cell lines. To evaluate CTEN promoter activity in mice and develop a new tissue specific Cre recombinase mouse model, we have established pCTEN-Cre:R26R mice by crossing R26R β-galactosidase reporter mice with pCTEN-Cre transgenic mice, in which the 327-bp cten promoter drives the expression of Cre recombinase. X-gal analysis has shown strong β-galactosidase activities in the prostate, brain, and few other tissues in pCTEN-Cre:R26R mice. Altogether, we have identified the promoter region of human cten gene and provided a useful tool for investigating cell lineages and generating tissue-specific knockout or knockin mice.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California-Davis, Sacramento, CA 95817, USA.
authors.forename: Nien-Tsu
authors.initials: NT
authors.lastname: Chen
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Christopher
authors.initials: C
authors.lastname: Conley
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Liao
authors.forename: Shiao-Ya
authors.initials: SY
authors.lastname: Hong
authors.forename: Michelle
authors.initials: M
authors.lastname: Chen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Shih
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Chen
authors.forename: Fushing
authors.initials: F
authors.lastname: Hsieh
authors.forename: Su Hao
authors.initials: SH
authors.lastname: Lo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010802:Phylogeny; D011247:Pregnancy; D000070876:Tensins; D014158:Transcription, Genetic
chemical_list: D008840:Microfilament Proteins; C000603371:TNS4 protein, human; D000070876:Tensins; C000603393:Tns4 protein, mouse