Yatsuoka Toshimasa, Furukawa Toru, Sunamura Makoto, Matsuno Seiki, Horii Akira
Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi 980-8575, Japan.
Oncol Rep. 2004 Dec;12(6):1263-8.
Loss of heterozygosity (LOH) on 12q is frequently observed in primary pancreatic cancer, as well as in cancers of other tissues such as stomach and germ cells. LOH correlates with poor prognosis in patients suffering from pancreatic cancer. In quest of tumor suppressor genes in this region, we used bacterial artificial chromosome (BAC) clones to construct a contig to cover one of the two targeted regions previously detected in pancreatic cancer; this region, 12B, is no larger than 650-kb between D12S360 and D12S78 at 12q22-q23.1. While constructing a detailed physical map and placing expressed sequence-tags, we identified a novel human gene, TU12B1-TY. This gene consisted of at least 14 exons and harbored an open reading frame possibly encoding a 473 amino-acid protein. A motif prediction program revealed a transmembrane domain in its carboxyl terminus. Expression in human tissues was found in the brain, placenta, skeletal muscle, pancreas, testis, uterus, and small intestine. In 21 pancreatic cancer cell lines analyzed, we found no structural alteration but all of them showed reduced expression. The present results indicate that reduced function of TU12B1-TY may contribute to the development and/or progression of human pancreatic cancer.
12号染色体长臂杂合性缺失（LOH）在原发性胰腺癌以及其他组织如胃癌和生殖细胞癌中经常被观察到。LOH与胰腺癌患者的不良预后相关。为了寻找该区域的肿瘤抑制基因，我们使用细菌人工染色体（BAC）克隆构建了一个重叠群，以覆盖先前在胰腺癌中检测到的两个目标区域之一；这个区域，即12B，在12q22 - q23.1处，位于D12S360和D12S78之间，不超过650千碱基对。在构建详细的物理图谱并放置表达序列标签时，我们鉴定出一个新的人类基因，TU12B1 - TY。该基因至少由14个外显子组成，含有一个可能编码473个氨基酸蛋白质的开放阅读框。一个基序预测程序在其羧基末端发现了一个跨膜结构域。在人类组织中的表达见于脑、胎盘、骨骼肌、胰腺、睾丸、子宫和小肠。在分析的21个胰腺癌细胞系中，我们未发现结构改变，但所有细胞系均显示表达降低。目前的结果表明，TU12B1 - TY功能降低可能有助于人类胰腺癌的发生和/或进展。
