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Aberrant methylation of human L- and M-fructose 1,6-bisphosphatase genes in cancer |
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| Authors: | Bigl Marina Jandrig Burkhard Horn Lars-Christian Eschrich Klaus |
| Affiliation: | a Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany b Max Delbrück Center for Molecular Medicine, Berlin, Germany c Institute of Pathology, Division of Gynecologic and Perinatal Pathology, University of Leipzig, Leipzig, Germany |
| Abstract: | A possible epigenetic regulation of the two isoenzymes of fructose 1,6-bisphosphatase (FBPase) was studied in liver, muscle, mamma, breast cancer and in different cancer cell lines. Results obtained after bisulfite sequencing revealed a different CpG methylation of both promoters in liver, muscle and breast tissue which is putatively involved in the cell-type specific gene expression of the two enzymes. In tumor cell lines, demethylation with 5-aza-deoxycytidine activated the expression of both isoenzymes. Additional inhibition of histone deacetylase with trichostatin A further increased FBPase mRNA concentrations. Since cancers typically have an abnormal energy metabolism and exhibit a low gluconeogenic phenotype, it was studied whether promoter methylation contributes to the decreased expression of FBPase in breast cancer. When non-malignant and malignant tissue samples from the same patient were compared a correlation between an increase of FBPase promoter methylation and a decrease of FBPase mRNA levels was observed. |
| Keywords: | Breast cancer Cell line DNA methylation Fructose 1,6-bisphosphatase Gene expression Gluconeogenesis Promoter Tissue-specific expression |
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