Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues
Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues
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DOI：
10.1002/ijc.11050
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发表时间：
2003-06-10
影响因子：
6.4
通讯作者：
Harada, S
中科院分区：
文献类型：
--
作者：
Hisatomi, H;Kohno, N;Harada, S
人孕酮受体（PR）是一种配体激活的核转录因子，介导孕酮在靶组织中的作用。我们在乳腺癌组织中发现了一种新的PR mRNA的选择性剪接变体（ASV）。缺失的转录本的特征在于外显子6（PR δ 6/2 ASV）中52 bp的框外缺失。PR δ 6/2 ASV mRNA导致激素受体配体结合域区域的部分缺陷，其中蛋白质核心缺失保守残基。为了阐明PR δ 6/2 ASV的临床意义，我们使用RT-PCR研究了该ASV在乳腺癌患者的非癌组织和癌组织中的表达。在39例乳腺癌患者的癌组织中有24例（61.5%）和39例非癌组织中有3例（7.7%）检测到新的PR δ 6/2 mRNA。PR δ 6/2 ASV mRNA在乳腺癌组织中的表达明显高于非癌组织（p < 0.0001），提示PR δ 6/2表达与乳腺癌的发生有关。我们的观察可能为乳腺癌的基因诊断提供一种新的策略。(C)2003 Wiley-Liss，Inc.
The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor that mediates progesterone action in target tissues. We found a novel alternatively spliced variant (ASV) of the PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out-of-frame deletion of 52 bp in exon 6 (PR delta6/2 ASV). The PR delta6/2 ASV mRNA results in a partial defect in the region of the ligand-binding domain of the hormone receptor, where conserved residues are missing from the core of the protein. To clarify the clinical significance of the PR delta6/2 ASV, we investigated the expression of this ASV in noncancerous and cancerous tissues from patients with breast cancer using RT-PCR. The novel PR delta6/2 mRNA was detected in 24 of 39 (61.5%) cancerous tissues and in 3 of 39 (7.7%) noncancerous tissues from patients with breast cancer. PR delta6/2 ASV mRNA was expressed more frequently in breast cancer tissues than in noncancerous tissues (p < 0.0001), which suggests a possible relationship between the expression of PR delta6/2 and breast cancer. Our observations may provide a novel strategy for the genetic diagnosis of breast cancer. (C) 2003 Wiley-Liss, Inc.