title: Altered gene expression profile after exposure to transforming growth factor β1 in the 253J human bladder cancer cell line.
abstract: OBJECTIVE
  Transforming growth factor β1 (TGF-β1) inhibits the growth of bladder cancer cells and this effect is prominent and constant in 253J bladder cancer cells. We performed a microarray analysis to search for genes that were altered after TGF-β1 treatment to understand the growth inhibitory action of TGF-β1.
  
  
  METHODS
  253J bladder cancer cells were exposed to TGF-β1 and total RNA was extracted at 6, 24, and 48 hours after exposure. The RNA was hybridized onto a human 22K oligonucleotide microarray and the data were analyzed by using GeneSpring 7.1.
  
  
  RESULTS
  In the microarray analysis, a total of 1,974 genes showing changes of more than 2.0 fold were selected. The selected genes were further subdivided into five highly cohesive clusters with high probability according to the time-dependent expression pattern. A total of 310 genes showing changes of more than 2.0 fold in repeated arrays were identified by use of simple t-tests. Of these genes, those having a known function were listed according to clusters. Microarray analysis showed increased expression of molecules known to be related to Smad-dependent signal transduction, such as SARA and Smad4, and also those known to be related to the mitogen-activated protein kinase (MAPK) pathway, such as MAPKK1 and MAPKK4.
  
  
  CONCLUSIONS
  A list of genes showing significantly altered expression profiles after TGF-β1 treatment was made according to five highly cohesive clusters. The data suggest that the growth inhibitory effect of TGF-β1 in bladder cancer may occur through the Smad-dependent pathway, possibly via activation of the extracellular signal-related kinase 1 and Jun amino-terminal kinases Mitogen-activated protein kinase pathway.
authors.affiliation: Department of Urology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea. ; Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Changho
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Urology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Doo Sang
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Urology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Jeon
authors.affiliation: Department of Urology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D052138:Genes, Neoplasm; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: Cell line; Gene expression; Microarray analysis; Transforming growth factor beta; Urinary bladder neoplasms