MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer.
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.


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.


CONCLUSIONS
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.
Bera
T K
TK
Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes ofHealth, Bethesda, Maryland 20892-4255, USA.
Lee
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S
Salvatore
G
G
Lee
B
B
Pastan
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I
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D030561:Databases, Nucleic Acid; D005091:Exons / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005810:Multigene Family; D016415:Sequence Alignment; D012984:Software; D013737:Testis / Q000502:physiology; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C435500:ABCC11 protein, human