Nagao Kumi, Kohno Norio, Wakita Kazuyuki, Hikiji Kazumasa, Yamamoto Shigeki, Hirata Hiroyuki, Hisatomi Hisashi
Center for Molecular Biology and Cytogenetics, SRL, Inc, Tokyo 191-0002, Japan.
Oncol Rep. 2003 Mar-Apr;10(2):305-8.
We identified a novel alternatively spliced isoform of PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out-of-frame deletion of 437 bp, corresponding to the complete loss of exons 4 and 6 (PR delta4+6 ASV). PR delta4+6 ASV will result in a partial defect in the region of the ligand-binding domain of hormone receptors, suggesting that the conserved residues are missing from the core of the protein. In the limited number of samples studied, a novel PR delta4+6 mRNA was detected in 1 of 45 (2.2%) non-cancerous tissues of patients with breast cancer, in 5 of 45 (11.1%) cancerous tissues of patients with breast cancer. Loss of both exons 4 and 6 will be induced by incomplete splicing and/or repair mechanism. Further studies are necessary to establish the biological significance of this alternative splicing. The expressions of ASVs that induced the mimic PR transcripts need to be considered when designing strategies for regulation analysis of the PR gene.
我们在乳腺癌组织中鉴定出一种新的PR mRNA可变剪接异构体。缺失的转录本特征为437 bp的框外缺失，对应于外显子4和6的完全缺失（PR delta4+6 ASV）。PR delta4+6 ASV将导致激素受体配体结合域区域出现部分缺陷，这表明该蛋白核心区域的保守残基缺失。在所研究的有限数量样本中，在45例乳腺癌患者的1例（2.2%）非癌组织以及45例乳腺癌患者的5例（11.1%）癌组织中检测到一种新的PR delta4+6 mRNA。外显子4和6的缺失将由不完全剪接和/或修复机制诱导。有必要进一步研究以确定这种可变剪接的生物学意义。在设计PR基因调控分析策略时，需要考虑诱导模拟PR转录本的ASV的表达情况。
