title: Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer.
abstract: Malignant tumors degrade glucose to lactate even in the presence of oxygen via the pentose phosphate pathway (ppp). The non-oxidative part of the ppp is controlled by thiamine-dependant transketolase enzyme reactions. Overexpression of the transketolase-like-1-gene (TKTL1) in urothelial and colorectal cancer is associated with poor patient outcome. We analyzed the expression of the TKTL1 protein in a retrospective institution-based patient cohort with invasive breast cancer by immunohistochemical analysis of 124 paraffin-embedded breast cancer tissues. Our study revealed TKTL1 expression in 86% of breast cancer specimens with 45% showing high expression levels. In contrast, only 29% of corresponding non-neoplastic breast tissues were TKTL1 immunopositive, including 9% with high expression levels. High expression levels of TKTL1 correlated significantly to Her2/neu overexpression (p=0.015). However, TKTL1 expression failed to reach statistical significance for other common prognostic parameters. In contrast to recent data for e.g. colorectal cancer TKTL1 overexpression did not correlate to patient outcome and survival. However, in the context of novel insights into TKTL1-related tumor metabolism and the high proportion of TKTL1 overexpressing breast cancers, this enzyme represents a potential candidate for targeted inhibition of tumor growth in this tumor entity.
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors.forename: Martha
authors.initials: M
authors.lastname: Földi
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.forename: Lidija
authors.initials: L
authors.lastname: Bau
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.forename: Dirk
authors.initials: D
authors.lastname: Watermann
authors.forename: Gerald
authors.initials: G
authors.lastname: Gitsch
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Coy
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D007150:Immunohistochemistry; D014174:Transketolase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C505431:TKTL1 protein, human; D014174:Transketolase