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5 June 1997, Volume 14, Number 22, Pages 2729-2733
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Short report
Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein
Friederike Müeller-Pillasch1,a, Ulrike Lacher1, Christine Wallrapp1, Anne Micha1, Frank Zimmerhackl1, Horst Hameister2, Gabor Varga3, Helmut Friess4, Markus Büchler4, Hans Günther Beger5, Maya R Vila6, Guido Adler1 and Thomas M Gress1

1Department of Internal Medicine I, University of Ulm, Robert Koch Str 8, 89081 Ulm, Germany

2Department of Medical Genetics, University of Ulm, Ulm, Germany

3Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

4Department of Viszeral and Transplantation Surgery, Inselspital, University of Berne, Berne, Switzerland

5Department of Surgery, University of Ulm, Ulm, Germany

6Institut Municipal d'Investigacio Medicia, Universitat Autonoma de Barcelona, Barcelona, Spain

aAuthor for correspondence

Abstract

In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65 000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

Keywords

pancreatic cancer; KH-domain; RNA-binding; overexpression

Received 12 December 1999; revised 24 February 1999; accepted 25 February 1999
5 June 1997, Volume 14, Number 22, Pages 2729-2733
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