MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer.
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 approximately 25 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.
Bera
Tapan K
TK
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4264, USA.
Iavarone
Carlo
C
Kumar
Vasantha
V
Lee
Sanghyuk
S
Lee
Byungkook
B
Pastan
Ira
I
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014158:Transcription, Genetic
C435501:ABCC12 protein, human; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D012333:RNA, Messenger