Alteration of frizzled expression in renal cell carcinoma.
To evaluate the involvement of frizzled receptors (Fzds) in oncogenesis, we investigated mRNA expression levels of several human Fzds in more than 30 different human tumor samples and their corresponding (matched) normal tissue samples, using real-time quantitative PCR. We observed that the mRNA level of Fzd5 was markedly increased in 8 of 11 renal carcinoma samples whilst Fzd8 mRNA was increased in 7 of 11 renal carcinoma samples. Western blot analysis of crude membrane fractions revealed that Fzd5 protein expression in the matched tumor/normal kidney samples correlated with the observed mRNA level. Wnt/beta-catenin signaling pathway activation was confirmed by the increased expression of a set of target genes. Using a kidney tumor tissue array, Fzd5 protein expression was investigated in a broader panel of kidney tumor samples. Fzd5 membrane staining was detected in 30% of clear cell carcinomas, and there was a strong correlation with nuclear cyclin D1 staining in the samples. Our data suggested that altered expression of certain members of the Fzd family, and their downstream targets, could provide alternative mechanisms leading to activation of the Wnt signaling pathway in renal carcinogenesis. Fzd family members may have a role as a biomarker.
Janssens
Nico
N
Department of Biochemistry, University of Antwerp, Wilrijk, Belgium. njansse9@prdbe.jnj.com
Andries
Luc
L
Janicot
Michel
M
Perera
Tim
T
Bakker
Annette
A
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D017931:DNA Primers; D015342:DNA Probes; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D051157:Frizzled Receptors; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D015342:DNA Probes; D005136:Eye Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; C498589:FZD5 protein, human; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins