title: Hypoxia induces the expression of transketolase-like 1 in human colorectal cancer.
abstract: OBJECTIVE
  Transketolase-like (TKTL) 1 is one of the key enzymes for anaerobic sugar degradation even in the presence of oxygen (aerobic glycolysis). Transketolase-dependent reactions supply malignant tumors with ribose and NADPH. Therefore, TKTL1 activity could be crucial for tumor proliferation and survival. The aim of the study was to evaluate the expression of TKTL1 in colorectal cancer (CRC) and its regulation under hypoxic conditions.
  
  
  METHODS
  We studied TKTL1 mRNA and protein expression in CRC cell lines and human CRC biopsies by quantitative real-time PCR, Western blotting and immunohistochemistry. Regulation of TKTL1 under oxygen depletion was analyzed by cultivating cells either in a three-dimensional spheroid model or in a hypoxia incubator chamber.
  
  
  RESULTS
  TKTL1 mRNA was heterogeneously expressed in monolayers of cells with high levels in HT-29 and SW480. TKTL1 protein was also clearly detectable in HT-29 and SW480. Hypoxia-inducible factor (HIF)-1α protein expression correlated with TKTL1 protein expression in SW480 spheroids over time. On the one hand, induction of hypoxia in T84 spheroids did not induce TKTL1; on the other hand, hypoxia by incubation at 1% O₂ in a hypoxia incubator chamber clearly showed an upregulation of TKTL1. In 50% of CRC patients, TKTL1 protein expression was upregulated in tumor compared to non-tumor tissue. The immunohistochemical staining of TKTL1 in CRC patient samples resulted in 14 positive and 30 negative samples.
  
  
  CONCLUSIONS
  TKTL1 expression correlated with HIF-1α protein expression and was induced upon hypoxic conditions which could facilitate energy supply to tumors under these circumstances.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Bentz
authors.forename: A
authors.initials: A
authors.lastname: Cee
authors.forename: E
authors.initials: E
authors.lastname: Endlicher
authors.forename: K A
authors.initials: KA
authors.lastname: Wojtal
authors.forename: A
authors.initials: A
authors.lastname: Naami
authors.forename: T
authors.initials: T
authors.lastname: Pesch
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: P
authors.initials: P
authors.lastname: Schubert
authors.forename: M
authors.initials: M
authors.lastname: Fried
authors.forename: A
authors.initials: A
authors.lastname: Weber
authors.forename: J F
authors.initials: JF
authors.lastname: Coy
authors.forename: S
authors.initials: S
authors.lastname: Goelder
authors.forename: R
authors.initials: R
authors.lastname: Knüchel
authors.forename: M
authors.initials: M
authors.lastname: Hausmann
authors.forename: G
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D019073:HT29 Cells; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D014174:Transketolase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C505431:TKTL1 protein, human; D014174:Transketolase