title: A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines.
abstract: OBJECTIVE
  To identify genes important in prostate cancer metastatic to bone. Bone-specific metastasis is a common feature of prostate cancer and a significant cause of morbidity.
  
  
  METHODS
  To identify factors involved in organ-specific metastasis, we used cDNA microarray analysis to compare a bone-derived cell line, VCaP, with a soft tissue-derived cell line, DuCaP. Both cell lines were derived from the same patient and spontaneously passaged.
  
  
  RESULTS
  Forty-five genes were differentially expressed, and only seven of these also had increased expression in VCaP compared with normal prostatic tissue. Of these, protease-activated receptor 1 (PAR1) was verified as having increased expression by reverse transcriptase-polymerase chain reaction and Northern blot analysis, as well as by immunohistochemistry. PAR1 expression in a panel of prostate cancer cell lines demonstrated increased expression in those cell lines derived from bone metastases. Alpha-thrombin stimulation of the VCaP cells produced a dose-dependent mobilization of intracellular calcium compared with DuCaP, suggesting that PAR1 expressed on the VCaP prostate cancer cell line is functional.
  
  
  CONCLUSIONS
  These data indicate that a functional PAR1 is expressed on prostate cancer cell lines. The prostate cancer cell lines expressing PAR1 appear to have an association with increased bone metastases.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0946, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Chay
authors.forename: Carlton R
authors.initials: CR
authors.lastname: Cooper
authors.forename: James D
authors.initials: JD
authors.lastname: Gendernalik
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Alvin H
authors.initials: AH
authors.lastname: Schmaier
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary*; D002118:Calcium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000235:genetics* / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D006490:Hemostatics; D009363:Neoplasm Proteins; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin; D002118:Calcium