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通过可变剪接产生的截短型人内皮素受体A及其在黑色素瘤中的表达。

Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma.

作者信息

Zhang Y F, Jeffery S, Burchill S A, Berry P A, Kaski J C, Carter N D

机构信息

Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.

出版信息

Br J Cancer. 1998 Nov;78(9):1141-6. doi: 10.1038/bjc.1998.643.

DOI:10.1038/bjc.1998.643
PMID:9820169
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2062989/
Abstract

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs.

摘要

在本研究中,采用逆转录聚合酶链反应扩增人内皮素受体A(ETA)和ETB受体mRNA。发现了一种缺失外显子3和4的截短型ETA受体转录本。这两个外显子的缺失导致受体缺失109个氨基酸。截短型受体在所有检测的组织和细胞中均有表达,但表达水平有所不同。在黑色素瘤细胞系和黑色素瘤组织中,截短型受体基因是主要类型,而野生型ETA在其他组织中占主导地位。通过Northern印迹法在黑色素瘤细胞系中鉴定出一个1.9 kb的ETA转录本,其比先前报道的心脏和其他组织中的转录本(4.3 kb)小得多。将截短型和野生型ETA受体的cDNA编码区稳定转染至中国仓鼠卵巢(CHO)细胞中。转染了截短型ETA受体的CHO细胞对内皮素1(ET-1)或内皮素3(ET-3)不显示结合亲和力。这种截短型ETA受体的功能和生物学意义尚不清楚,但它可能对细胞对内皮素的反应具有调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/f0b302e17ec5/brjcancer00013-0027-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/0cfac1cd2535/brjcancer00013-0026-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/bbefaae79d17/brjcancer00013-0026-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/811ea684e84e/brjcancer00013-0026-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/43e1014883f7/brjcancer00013-0027-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/f0b302e17ec5/brjcancer00013-0027-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/0cfac1cd2535/brjcancer00013-0026-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/bbefaae79d17/brjcancer00013-0026-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/811ea684e84e/brjcancer00013-0026-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/43e1014883f7/brjcancer00013-0027-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dded/2062989/f0b302e17ec5/brjcancer00013-0027-b.jpg

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本文引用的文献

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Development. 1996 Dec;122(12):3911-9. doi: 10.1242/dev.122.12.3911.
2
Mutant isoforms of the anti-Müllerian hormone type II receptor are not expressed at the cell membrane.抗苗勒管激素II型受体的突变异构体不在细胞膜上表达。
J Biol Chem. 1996 Nov 29;271(48):30571-5. doi: 10.1074/jbc.271.48.30571.
3
Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing.
内皮素受体B拮抗剂在体外和体内均可抑制人黑色素瘤细胞的生长并诱导其细胞死亡。
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11496-500. doi: 10.1073/pnas.96.20.11496.
通过可变剪接产生的5-羟色胺2C受体短变体的鉴定、分子克隆及分布
Mol Pharmacol. 1996 Oct;50(4):799-807.
4
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