Müeller-Pillasch F, Lacher U, Wallrapp C, Micha A, Zimmerhackl F, Hameister H, Varga G, Friess H, Büchler M, Beger H G, Vila M R, Adler G, Gress T M
Department of Internal Medicine I, University of Ulm, Germany.
Oncogene. 1997 Jun 5;14(22):2729-33. doi: 10.1038/sj.onc.1201110.
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.
在先前一项针对胰腺癌中差异表达基因的大规模筛选中，我们鉴定出一个在癌症中高度过表达的基因，该基因编码一种具有四个K-同源（KH）结构域的新型蛋白质。KH结构域存在于一部分RNA结合蛋白中，包括前体mRNA结合（hnRNP）K蛋白和脆性X智力低下基因产物（FMR1）。通过荧光原位杂交（FISH），将鉴定出的名为koc（癌症中过表达的含KH结构域蛋白）的基因定位到7号染色体p11.5区域。两个假基因定位于6号和11号染色体上。克隆的koc cDNA具有一个250 bp的5'-非翻译区、一个1740 bp的开放阅读框和一个2168 bp的3'-非翻译区。koc富含AU的3'-非翻译区包含八个AUUUA和四个AUUUUUA重复基序。推导的含有580个氨基酸的koc蛋白的相对分子质量（Mr）约为65,000（65K）。与正常胰腺组织和慢性胰腺炎组织相比，koc转录本在胰腺癌细胞系和胰腺癌组织中高度过表达。在其他人类肿瘤的组织样本中也发现了高水平的表达。由于KH结构域已被证明参与RNA合成和代谢的调控，我们推测koc可能通过干扰转录和/或转录后过程在肿瘤细胞增殖调控中发挥作用。然而，koc在人类肿瘤细胞中的精确作用尚不清楚，仍有待阐明。
