MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer
MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer
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DOI：
10.1007/bf03401856
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发表时间：
2001-08-01
影响因子：
5.7
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Bera, TK;Lee, S;Pastan, I
背景：随着人类基因组序列草图的完成，人们正致力于鉴定新的基因。我们已经开发了一种基于计算机的策略，利用EST数据库来识别新的基因，这些基因可能是癌症免疫治疗的目标，或者可能参与癌症的多步骤过程。材料和方法：利用我们基于计算机的筛选策略，我们确定了一组在乳腺癌中高度表达的表达序列标签（est）。Northern blot和逆转录聚合酶链反应（RT-PCR）分析表明，计算机生成的聚类具有组织特异性，并与人类基因组序列进行比较，有助于分离出全长cDNA克隆。结果：我们发现了一个在乳腺癌中高表达的新基因。该基因在正常乳腺和睾丸中表达水平中等，在肝脏、大脑和胎盘中表达水平极低。该基因有两个主要的转录本，分别为4.5 kb和4.1 kb。这个4.5 kb的转录本在乳腺癌中非常丰富，有一个1382个氨基酸的开放阅读框。预测的4.5 kb转录本蛋白序列显示其与多药耐药相关蛋白家族（MRP）成员MRP5具有高度同源性。据报道，MRP家族有7个成员；我们将该基因命名为MRP8 （ABCC11）。4.5 kb的MRP8转录本由31个外显子组成，位于染色体16q12.1上超过80.4 kb的基因组区域。在睾丸中发现了较小的4.1 kb MRP8转录本，可能在该基因的内含子6内启动。结论：atp结合盒转运蛋白超家族新成员MRP8 （ABCC11）的选择性表达可能成为治疗乳腺癌的分子靶点。
Background: With the completion of the human draft genome sequence, efforts are now devoted to identifying new genes. We have developed a computer-based strategy that utilizes the EST database to identify new genes that could be targets for the immunotherapy of cancer or could be involved in the multistep process of cancer.Materials and Methods: Utilizing our computer-based screening strategy, we identified a cluster of expressed sequence tags (ESTs) that are highly expressed in breast cancer. Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated the tissue specificity of the computer-generated cluster and comparison with the human genome sequence assisted in isolating a full-length cDNA clone.Results: We identified a new gene that is highly expressed in breast cancer. This gene is expressed at moderate levels in normal breast and testis and at very low levels in liver, brain, and placenta. The gene has two major transcripts of 4.5 kb and 4.1 kb. The 4.5-kb transcript is very abundant in breast cancer, and has an open reading frame of 1382 amino acids. The predicted protein sequence of the 4.5-kb transcript reveals that it has high homology with MRP5, a member of multidrug resistant-associated protein family (MRP). There are seven reported members in the MRP family; we designate this gene as MRP8 (ABCC11). The 4.5-kb MRP8 transcript consists of 31 exons and is located in a genomic region of over 80.4 kb on chromosome 16q12.1. The smaller 4.1-kb transcript of MRP8 is found in testis and may initiate within intron 6 of the gene.Conclusion: The selective expression of MRP8 (ABCC11), a new member of ATP-binding cassette transporter superfamily could be a molecular target for the treatment of breast cancer.