title: Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer.
abstract: OBJECTIVE
  To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer.
  
  
  METHODS
  Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and LPAR2.
  
  
  RESULTS
  Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson's correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM stage.
  
  
  CONCLUSIONS
  Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shida
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kodaka
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuiji
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D049349:Receptors, Lysosphingolipid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000081025:Sphingosine-1-Phosphate Receptors; D015854:Up-Regulation; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C000609550:LPAR2 protein, human; C477362:S1PR1 protein, human; C477522:S1PR2 protein, human; C577483:sphingosine-1-phosphate receptor-3, human
keywords: Carcinogenesis; Colorectal cancer; Lysophosphatidic acid receptor 2; Sphingosine 1-phosphate; Sphingosine kinase 1