Tandem duplication of the epidermal growth factor receptor tyrosine kinase and calcium internalization domains in A-172 glioma cells
Tandem duplication of the epidermal growth factor receptor tyrosine kinase and calcium internalization domains in A-172 glioma cells
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DOI：
10.1038/sj.onc.1202156
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发表时间：
1998-07-02
期刊：
影响因子：
8
通讯作者：
Castiglia, GJ
中科院分区：
文献类型：
--
作者：
Fenstermaker, RA;Ciesielski, MJ;Castiglia, GJ
表皮生长因子受体（EGFR）基因扩增和重排在恶性胶质瘤中频繁发生。重排也可能导致潜在致癌EGFR缺失突变体的表达。本文提供的数据表明，A-172神经胶质瘤细胞中存在EGFR的190 kDa突变形式，其与先前表征的缺失突变体基本不同。EC; FR样蛋白与170 kDa野生型EGFR一起沿着表达。它可以用EGFR的细胞外和细胞内区域的抗体检测到，但不与其他HER家族成员交叉反应。野生型和突变型受体在响应TGF α治疗时发生磷酸化，并与10.5 kb和11.5 kb EGFR相关转录物的表达相关。联合逆转录-聚合酶链反应（RT-PCR）鉴定了A-172细胞中编码酪氨酸激酶和钙内化（TK/CAIN）结构域（外显子18至26）的框内串联重复的独特转录物。这些结构域的重复与EGFR基因内含子26和17内潜在的v-myb和c-myb共有结合位点之间的特异性基因组重排相关，导致嵌合内含子的形成。
Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene occur frequently in malignant gliomas. Rearrangement may also lead to the expression of potentially oncogenic EGFR deletion mutants. Data presented here indicate the existence of a 190 kDa mutant form of the EGFR in A-172 glioma cells that is substantially different from the deletion mutants characterized previously. The EC;FR-like protein is expressed along with the 170 kDa wild type EGFR. It is detectable with antibodies to both extracellular and intracellular regions of the EGFR, but is not crossreactive with other HER-family members, The wild type and mutant receptors undergo phosphorylation in response to treatment with TGF alpha and are associated with expression of both 10.5 kb and 11.5 kb EGFR-related transcripts. Combined reverse transcription-polymerase chain reaction (RT-PCR) identifies a unique transcript in A-172 cells that encodes an in-frame, tandem duplication of both tyrosine kinase and calcium internalization (TK/CAIN) domains (exons 18 through 26). The duplication of these domains is associated with a specific genomic rearrangement between potential v-myb and c-myb consensus binding sites within introns 26 and 17 of the EGFR gene resulting in the formation of a chimeric intron.