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Absence of APOBEC-1 mediated mRNA editing in human carcinomas
J Greeve1, H Lellek, F Apostel
1Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Abstract:
The transgene expression of the catalytic subunit APOBEC-1 of the apo B mRNA editing enzyme-complex can cause hepatocellular carcinoma in mice and rabbits. It has been proposed that aberrant editing of mRNA may represent a novel oncogenic principle. This investigation aimed to define whether such aberrant hyperediting mediated by APOBEC-1 occurs in human carcinomas. Editing and hyperediting of apo B, NAT1 or NF1 mRNA was not identified in any of 28 resected tumor specimens, including hepatocellular, bile duct, gastric, colorectal, pancreatic adeno- and neuroendocrine, lung adeno-, medullary thyroid and breast carcinoma, soft tissue sarcoma and neuroblastoma. In most types of carcinoma, significant levels for full-length APOBEC-1 mRNA could not be detected. Low level expression of APOBEC-1 was found in colorectal and gastric carcinoma where most of the APOBEC-1 mRNA is inactivated by alternate splicing. The 'auxiliary' components of the apo B mRNA editing enzyme-complex are missing in many tumors including colorectal and gastric carcinoma, but are highly expressed in hepatocellular, lung adeno- and breast carcinoma all of which lack APOBEC-1. Taken together, either APOBEC-1 or the 'auxiliary' components of the apo B mRNA editing enzyme-complex or both are missing in human carcinomas resulting in the absence of mRNA editing. Currently, there is no evidence that aberrant editing mediated by APOBEC-1 contributes to the tumorigenesis of natural human carcinomas.
Insights
Aberrant mRNA editing by APOBEC-1 does not cause human carcinomas. Researchers found no evidence of APOBEC-1-mediated editing in 28 tumor types, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Transgene expression of APOBEC-1 can induce hepatocellular carcinoma in animal models.
- Aberrant mRNA editing has been proposed as a novel oncogenic mechanism.
Purpose of the Study:
- To investigate the occurrence of APOBEC-1-mediated aberrant mRNA hyperediting in human carcinomas.
- To determine if APOBEC-1 or its auxiliary components are involved in human cancer development.
Main Methods:
- Analysis of 28 human carcinoma specimens for mRNA editing and APOBEC-1 expression.
- Detection of editing and hyperediting of apo B, NAT1, and NF1 mRNA.
- Quantification of full-length APOBEC-1 mRNA and assessment of auxiliary component expression.
Main Results:
- No evidence of apo B, NAT1, or NF1 mRNA editing or hyperediting was found in any of the 28 human carcinoma types.
- Full-length APOBEC-1 mRNA was largely undetectable in most carcinomas.
- Low APOBEC-1 expression in some tumors showed inactivation by alternative splicing, and essential auxiliary components were often missing.
Conclusions:
- APOBEC-1 or its auxiliary components, or both, are absent or non-functional in human carcinomas, preventing mRNA editing.
- There is currently no evidence supporting a role for APOBEC-1-mediated aberrant editing in the tumorigenesis of natural human carcinomas.