Molecular cloning and expression of novel alternatively spliced cytochrome P450 2E1 mRNAs in humans.
Human cytochrome P450 2E1 (CYP2E1) is a phase I metabolizing enzyme. It is involved in the biotransformation of xenobiotics and endogenous substrates. Inter-individual genetic polymorphisms of the CYP2E1 gene are associated with different cancer diseases as well as alcohol and nicotine dependence. We report here for the first time three novel alternative spliced mRNA transcripts which are more frequently present in lung carcinoma cell lines as in hepatocyte cell lines. They are unexpected detectable in blood leukocytes from healthy volunteers but not in normal and cancerous lung tissue. The full-length wildtype transcript of CYP2E1 is described to be concomitant to an alternatively spliced mRNA transcript. Stimulation with CYP2E1-inducing agents did not change the splicing transcript pattern. The three splicing variants should lead to truncated non-functional proteins. Thus the genetic diversity of CYP2E1 is additionally extended at the transcriptional level of gene expression. The physiological role of the splicing variants is not known, yet, but they seem to be related to the carcinogenic property of the cell lines.
Bauer
Mario
M
Department of Human Exposure Research and Epidemiology, UFZ - Centre for Environmental Research Leipzig-Halle, Permoser street 15, 04318, Leipzig, Germany. mario.bauer@ufz.de
Herbarth
Olf
O
Aust
Gabi
G
Graebsch
Carolin
C
D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007962:Leukocytes; D008175:Lung Neoplasms; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D012333:RNA, Messenger; D015847:Interleukin-4; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1