Xiang Cunli, Sarid Ronit, Cazacu Simona, Finniss Susan, Lee Hae-Kyung, Ziv-Av Amotz, Mikkelsen Tom, Brodie Chaya
Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Health System, Detroit, MI 48202, USA.
Biochem Biophys Res Commun. 2007 Oct 26;362(3):612-8. doi: 10.1016/j.bbrc.2007.08.138. Epub 2007 Aug 31.
Here, we report the cloning and characterization of RTVP-1b, a novel splice variant of human RTVP-1, which was isolated from the U87 glioma cell line. Sequence analysis revealed that RTVP-1b contains an additional 71 base exon between exons 2 and 3 that is missing in RTVP-1, leading to a frame-shift and a different putative protein. The deduced protein was 237 amino acids in length, sharing the N-terminal 141 amino acids with RTVP-1. RT-PCR analysis demonstrated that RTVP-1b was expressed in a wide range of tissues and that its expression was different from that of RTVP-1. In contrast, RTVP-1 and RTVP-1b showed similar patterns of expression in astrocytic tumors; highly expressed in glioblastomas as compared to normal brains, low-grade astrocytomas and anaplastic oligodendrogliomas. Overexpression of RTVP-1b increased glioma cell proliferation but did not affect cell migration. Our results suggest that RTVP-1b represents a potential prognostic marker and therapeutic target in gliomas.
在此，我们报告了RTVP-1b的克隆与特性分析，RTVP-1b是从U87胶质瘤细胞系中分离出的人RTVP-1的一种新型剪接变体。序列分析显示，RTVP-1b在第2外显子和第3外显子之间含有一个额外的71个碱基的外显子，而RTVP-1中缺失该外显子，这导致了移码并产生了一种不同的假定蛋白质。推导的蛋白质长度为237个氨基酸，与RTVP-1共享N端的141个氨基酸。逆转录聚合酶链反应（RT-PCR）分析表明，RTVP-1b在多种组织中表达，且其表达与RTVP-1不同。相比之下，RTVP-1和RTVP-1b在星形细胞瘤中显示出相似的表达模式；与正常脑、低级别星形细胞瘤和间变性少突胶质细胞瘤相比，在胶质母细胞瘤中高表达。RTVP-1b的过表达增加了胶质瘤细胞的增殖，但不影响细胞迁移。我们的结果表明，RTVP-1b是胶质瘤中一种潜在的预后标志物和治疗靶点。
