MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer
MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer
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DOI：
10.1073/pnas.102187299
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发表时间：
2002-05-14
影响因子：
11.1
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Bera, TK;Iavarone, C;Pastan, I
结合基于计算机的筛选策略和功能基因组学，我们以前确定了MRP9（ABCC12），ATP结合盒（ABC）超家族的成员。我们现在表明，该基因有两个主要的成绩单4.5和1.3 kb。在乳腺癌、正常乳腺和睾丸中，MRP9基因转录物大小为4.5 kb，编码100 kDa蛋白。预测该蛋白质具有8个而不是12个跨膜区域。与密切相关的ABC家族成员相比，它缺乏跨膜结构域3、4、11和12以及第二个核苷酸结合结构域。在其他组织中，包括脑、骨骼肌和卵巢，转录本大小为1.3 kb。这个较小的转录本编码一个大小约为25 kDa的核苷酸结合蛋白。原位杂交研究表明，4.5 kb的转录本在乳腺癌的上皮细胞中表达。设计与蛋白质的氨基末端反应的抗肽抗体检测睾丸和乳腺癌细胞系的膜部分中的100 kDa蛋白质。由于4.5 kb RNA在乳腺癌中高度表达，而在基本正常组织中不表达，因此MRP9可能是乳腺癌免疫治疗的有用靶点。由于MRP9的两种变体的不寻常拓扑结构，我们推测它们可能具有与其他家族成员不同的功能。
Combining a computer-based screening strategy and functional genomics, we previously identified MRP9 (ABCC12), a member of the ATP-binding cassette (ABC) superfamily. We now show that the gene has two major transcripts of 4.5 and 1.3 kb. In breast cancer, normal breast, and testis, the MRP9 gene transcript is 4.5 kb in size and encodes a 100-kDa protein. The protein is predicted to have 8 instead of 12 membrane-spanning regions. When compared with closely related ABC family members, it lacks transmembrane domains 3, 4, 11, and 12 and the second nucleotide-binding domain. In other tissues including brain, skeletal muscle, and ovary, the transcript size is 1.3 kb. This smaller transcript encodes a nucleotide-binding protein of approximate to25 kDa in size. An in situ hybridization study shows that the 4.5-kb transcript is expressed in the epithelial cells of breast cancer. An antipeptide antibody designed to react with the amino terminus of the protein detects a 100-kDa protein in testis and the membrane fraction of a breast cancer cell line. Because the 4.5-kb RNA is highly expressed in breast cancer and not expressed at detectable levels in essential normal tissues, MRP9 could be a useful target for the immunotherapy of breast cancer. Because of the unusual topology of the two variants of MRP9, we speculate that they may have a different function from other family members.