title: Expression levels of PEPT1 and ABCG2 play key roles in 5-aminolevulinic acid (ALA)-induced tumor-specific protoporphyrin IX (PpIX) accumulation in bladder cancer.
abstract: BACKGROUND
  A detection method widely used of late in cancer surgery is 5-aminolevulinic acid-based photodynamic diagnosis (ALA-PDD), which relies on the tumor-specific accumulation of photosensitizing protoporphyrin IX (PpIX) after the administration of ALA. In this regard, we recently reported that peptide transporter PEPT1 and human ATP-binding cassette transporter ABCG2 are key players in regulating intracellular PpIX levels. In the present study, we re-evaluated in vivo the expression of genes involved in the porphyrin biosynthesis pathway.
  
  
  METHODS
  Using quantitative real-time (qRT)-PCR, we measured the mRNA levels in a clinical specimen of bladder cancer from a patient who had been subjected to ALA-PDD.
  
  
  RESULTS
  We confirmed that PEPT1 and ABCG2 are major contributors to the regulation of tumor-specific PpIX accumulation. qRT-PCR analysis revealed a predominantly high level of PEPT1 mRNA and a very low level of ABCG2 mRNA in the bladder cancer, corresponding to the roles of these genes in vitro. These findings were further confirmed by immunohistochemical studies with PEPT1- and ABCG2-specific antibodies.
  
  
  CONCLUSIONS
  The induction of PEPT1 gene and the suppression of ABCG2 gene expression are among the key molecular mechanisms underlying tumor-specific PpIX accumulation after the administration of ALA in bladder cancer.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B102 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hagiya
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Endo
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Okura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurabayashi
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Ogura
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000528:radiation effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D000074011:Peptide Transporter 1; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D027981:Symporters / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D000074011:Peptide Transporter 1; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C082186:SLC15A1 protein, human; D027981:Symporters; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid; ABCG2; Bladder cancer; PEPT1; Photodynamic diagnosis; Protoporphyrin IX