Bera Tapan K, Zimonjic Drazen B, Popescu Nicholas C, Sathyanarayana Bangalore K, Kumar Vasantha, Lee Byungkook, Pastan Ira
Laboratories of Molecular Biology and Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16975-80. doi: 10.1073/pnas.262655399. Epub 2002 Dec 10.
We have identified a gene located on chromosomes 21 that is expressed in normal and neoplastic prostate, and in normal testis, ovary, and placenta. We name this gene POTE (expressed in prostate, ovary, testis, and placenta). The POTE gene has 11 exons and 10 introns and spans approximately equal 32 kb of chromosome 21q11.2 region. The 1.83-kb mRNA of POTE encodes a protein of 66 kDa. Ten paralogs of the gene have been found dispersed among eight different chromosomes (2, 8, 13, 14, 15, 18, 21, and 22) with preservation of ORFs and splice junctions. The synonymous:nonsynonymous ratio indicates that the genes were duplicated rather recently but are diverging at a rate faster than the average for other paralogous genes. In prostate and in testis, at least five different paralogs are expressed. In situ hybridization shows that POTE is expressed in basal and terminal cells of normal prostate epithelium. It is also expressed in some prostate cancers and in the LnCAP prostate cancer cell line. The POTE protein contains seven ankyrin repeats between amino acids 140 and 380. Expression of POTE in prostate cancer and its undetectable expression in normal essential tissues make POTE a candidate for the immunotherapy of prostate cancer. The existence of a large number of closely related but rapidly diverging members, their location on multiple chromosomes and their limited expression pattern suggest an important role for the POTE gene family in reproductive processes.
我们已经鉴定出一个位于21号染色体上的基因,该基因在正常前列腺组织、肿瘤性前列腺组织、正常睾丸、卵巢和胎盘中均有表达。我们将此基因命名为POTE(在前列腺、卵巢、睾丸和胎盘中表达)。POTE基因有11个外显子和10个内含子,跨越21号染色体q11.2区域约32kb。POTE的1.83kb mRNA编码一个66kDa的蛋白质。已发现该基因的10个旁系同源基因分散在8条不同的染色体(2、8、13、14、15、18、21和22)上,其开放阅读框和剪接位点得以保留。同义突变与非同义突变的比例表明这些基因是最近才复制的,但分化速度比其他旁系同源基因的平均速度要快。在前列腺和睾丸中,至少有5个不同的旁系同源基因表达。原位杂交显示POTE在正常前列腺上皮的基底细胞和终末细胞中表达。它也在一些前列腺癌和LnCAP前列腺癌细胞系中表达。POTE蛋白在氨基酸140至380之间含有7个锚蛋白重复序列。POTE在前列腺癌中的表达以及在正常重要组织中无法检测到的表达,使其成为前列腺癌免疫治疗的一个候选靶点。大量密切相关但快速分化的成员的存在、它们在多条染色体上的定位以及有限的表达模式表明POTE基因家族在生殖过程中具有重要作用。