Carcinogenesis, Vol. 20, No. 6, 985-989,
June 1999
© 1999 Oxford University Press
Cancer Biology |
Impairment of peroxisomal biogenesis in human colon carcinoma
Institut für Anatomie und Zellbiologie II, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany,
1 Chirurgische Universitätsklinik, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany and
2 Anatomisches Institut, Pestalozzistrasse 20, CH-4056 Basel, Switzerland
Peroxisomes and the activities of their enzymes have been reported to be significantly reduced in various types of tumors including the colon carcinoma. Therefore, the present study was designed to investigate the gene expression of several peroxisomal proteins in human colon carcinoma and additionally those of the peroxisome proliferator activated receptor 
(PPAR) and PEX5, a receptor protein involved in the import of most peroxisomal matrix proteins. Samples from adenocarcinomas and adjacent normal colon were analyzed by immunohistochemistry and western blotting. The mRNA content was assessed by a novel sensitive dot blot RNase protection assay and northern blotting. By immunohistochemistry, peroxisomes were distinctly visualized in normal colonocytes but were not detected in colon carcinoma cells. The protein levels of catalase (CAT), acyl-CoA oxidase as well as the 22 and 70 kDa peroxisomal membrane proteins (PMP22 and PMP70) were all significantly decreased in carcinomas. The corresponding mRNAs for CAT and PMP70, however, were unchanged. In contrast, the mRNA of PEX5 was significantly increased. The expression of PPAR was not altered in tumors, neither at protein nor mRNA levels. These observations show that the reduction of peroxisomes and their proteins in colon carcinoma is not due to a generalized reduction of transcription of their genes. It seems more likely that this phenomenon is regulated at a post-transcriptional or translational level. Alternatively, and more likely, an impairment of the biogenesis of the organelle could account for the paucity of peroxisomes in colon carcinoma.
Abbreviations: AOX, acyl-CoA oxidase; CAT, catalase; PMP22, 22 kDa peroxisomal membrane protein; PMP70, 70 kDa peroxisomal membrane protein; PPAR, peroxisome proliferator activated receptor.
3 To whom correspondence should be addressed Email: beier{at}ubaclu.unibas.ch
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