title: Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma.
abstract: BACKGROUND
  The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer.
  
  
  METHODS
  To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting.
  
  
  RESULTS
  Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors.
  
  
  CONCLUSIONS
  These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.
authors.forename: Hironori
authors.initials: H
authors.lastname: Betsunoh
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: Daisaku
authors.initials: D
authors.lastname: Nishihara
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Hideo
authors.initials: H
authors.lastname: Yuki
authors.forename: Akinori
authors.initials: A
authors.lastname: Masuda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yashi
authors.forename: Yoshitatsu
authors.initials: Y
authors.lastname: Fukabori
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. kamait@dokkyomed.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000378:metabolism
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; D012333:RNA, Messenger; D038601:Ribosomal Protein S6