title: Identification of the rat homologue of KAI1 and its expression in Dunning rat prostate cancers.
abstract: BACKGROUND
  We previously isolated the human KAI1 gene encoding a transmembrane protein which suppresses metastatic ability in Dunning R3327 AT6.1 rat prostate cancer cells when transfected into these cells. The AT6.1 subline is one of the more aggressive sublines among the Dunning R-3327 system of rat prostate cancers. This raises the issue of whether downregulation of KAI1 expression consistently occurs during the acquisition of high metastatic ability by members of the Dunning system of rat prostate cancers.
  
  
  METHODS
  To investigate this possibility, the rat homologue of the KAI1gene was identified, using a combination of cDNA library screening and 5'-RACE and DNA sequencing. Based on this information, a rat-specific cDNA probe was developed and used for Northern blot analysis of KAI1 expression in normal rat tissues and a series of sublines of Dunning R3327 cells that vary widely in their metastatic abilities.
  
  
  RESULTS
  The rat KAI1 gene encoded a protein of 266 amino acids which has 77% identity to the human KAI1 protein. In normal tissues, KAI1 is expressed predominantly as a 2.0-kb-sized transcript. Several tissues (e.g., skeletal muscle and prostate) also express a minor 1.8-kb-sized RNA. Northern blot analysis of a series of Dunning sublines demonstrated that all sublines expressed both the 2.0- and 1.8-kb KAI1 RNA transcripts. However, quantitative levels of the 2.0- vs. 1.8-kb KAI1 RNA were variable among sublines. Downregulation of expression of the 2.0-kb KAI1 transcript was statistically correlated with the acquisition of high metastatic ability within this system of prostate cancer sublines. In contrast, the 1.8-kb transcript was upregulated in all of the more aggressive sublines, but this enhanced expression was not specifically correlated with metastatic ability.
  
  
  CONCLUSIONS
  These studies demonstrated that downregulation of the 2.0-kb KAI1 mRNA is associated with the acquisition of high metastatic ability by prostate cancer cells.
authors.affiliation: Oncology Center, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: J T
authors.initials: JT
authors.lastname: Dong
authors.forename: A C
authors.initials: AC
authors.lastname: Gao
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: J T
authors.initials: JT
authors.lastname: Isaacs
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005544:Forecasting; D006801:Humans; D051861:Kangai-1 Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000556:secondary; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; C497688:CD82 protein, human; C497690:Cd82 protein, rat; D018076:DNA, Complementary; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger