Line Aija, Slucka Zane, Stengrevics Aivars, Li Geng, Rees Robert C
Biomedical Research and Study Center, University of Latvia, Riga, Latvia.
Cancer Genet Cytogenet. 2002 Nov;139(1):78-83. doi: 10.1016/s0165-4608(02)00607-6.
Transforming acidic coiled-coil (TACC) proteins are centrosome and microtubule-associated proteins that are essential for mitotic spindle function. We identified TACC1 as an immunogenic protein and a potential tumor antigen by applying serological identification of antigens by recombinant expression cloning (SEREX) technique to screen a gastric cancer cDNA library. The 5'RLM-RACE and reverse transcriptase polymerase chain reaction analyses revealed at least six different transcript variants of TACC1 with variable transcription start sites and alternative exon usage (designated TACC1-A-TACC1-F). All transcripts differ in their 5' ends but share an identical 3' region encoding coiled-coil domain. Four transcripts were universally expressed in all normal tissues analyzed but TACC1-D and TACC1-F showed a restricted expression pattern. TACC1-F, a transcript representing the SEREX-identified cDNA clone, was predominantly expressed in brain and gastric tumors to a similar level. TACC1-D was only weakly detectable in kidney and colon but not in other normal tissues, while a relatively strong expression was observed in 50% of gastric cancer tissue samples analyzed. These transcript variants are generated possibly as a result of alterations in efficiency and pattern of alternative splicing; these isoforms may represent genetic markers, for example TACC1-D for gastric cancer. We also propose that inappropriate expression of the isoforms in gastric cancer cells might result in dysfunction of TACC1 thus contributing to the genetic instability.
转化酸性卷曲螺旋（TACC）蛋白是与中心体和微管相关的蛋白，对有丝分裂纺锤体功能至关重要。我们通过应用重组表达克隆血清学抗原鉴定（SEREX）技术筛选胃癌cDNA文库，将TACC1鉴定为一种免疫原性蛋白和潜在的肿瘤抗原。5'RLM-RACE和逆转录聚合酶链反应分析显示，TACC1至少有六种不同的转录变体，其转录起始位点可变且外显子使用方式不同（命名为TACC1-A至TACC1-F）。所有转录本的5'端不同，但共享一个编码卷曲螺旋结构域的相同3'区域。四种转录本在所有分析的正常组织中均普遍表达，但TACC1-D和TACC1-F呈现出受限的表达模式。TACC1-F是代表SEREX鉴定的cDNA克隆的转录本，在脑和胃肿瘤中表达水平相似且占主导。TACC1-D在肾脏和结肠中仅能微弱检测到，在其他正常组织中未检测到，而在50%的分析胃癌组织样本中观察到相对较强的表达。这些转录变体可能是由于可变剪接效率和模式的改变而产生的；这些异构体可能代表遗传标记，例如胃癌的TACC1-D。我们还提出，异构体在胃癌细胞中的不适当表达可能导致TACC1功能障碍，从而导致基因不稳定。
