Expression of Dominant Negative Form of PAX4 in Human Insulinoma

The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in...

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Veröffentlicht in:Biochemical and biophysical research communications 2001-03, Vol.282 (1), p.34-40
Hauptverfasser: Miyamoto, Takahide, Kakizawa, Tomoko, Ichikawa, Kazuo, Nishio, Shinichi, Kajikawa, Shoji, Hashizume, Kiyoshi
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container_end_page 40
container_issue 1
container_start_page 34
container_title Biochemical and biophysical research communications
container_volume 282
creator Miyamoto, Takahide
Kakizawa, Tomoko
Ichikawa, Kazuo
Nishio, Shinichi
Kajikawa, Shoji
Hashizume, Kiyoshi
description The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.
doi_str_mv 10.1006/bbrc.2001.4552
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Amino Acid Sequence
Animals
Base Sequence
Cricetinae
Gene Expression Regulation
Genes, Dominant
Homeodomain Proteins - chemistry
Homeodomain Proteins - genetics
Humans
insulin promoter
insulinoma
Insulinoma - genetics
Insulinoma - pathology
Molecular Sequence Data
Paired Box Transcription Factors
pancreatic β-cell
PAX4
PAX4 variant
RNA Splicing
RNA, Messenger - genetics
transcription
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription, Genetic
Tumor Cells, Cultured
title Expression of Dominant Negative Form of PAX4 in Human Insulinoma
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