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Identification of ABCA5 as a tissue and urine diagnostic marker for prostatic intraepithelial epithelial or PIN
Journal article   Peer reviewed

Identification of ABCA5 as a tissue and urine diagnostic marker for prostatic intraepithelial epithelial or PIN

M. E. Stearns, Y. Hu, M. Wang and K. Veverka
Journal of clinical oncology, v 24(18_suppl), pp 10089-10089
20 Jun 2006
DOI: https://doi.org/10.1200/jco.2006.24.18_suppl.10089

Abstract

10089 Background: Bostwick and colleagues have suggested that prostatic intraepithelial neoplasia or PIN is the precursor of prostate cancer and that a significant percentage of men with PIN develop prostate cancer (Sakr, 1994; Bostwick, 1995b; Arakawa, 1995; Qian, 1995; Qian, 1997). Currently there are no diagnostic markers for PIN. Methods and Results: Recently, we have developed ‘DNA-protein’ binding assays for the identification of novel transcriptional regulatory proteins associated with PIN glands. Electrophoretic mobility assays (EMSAs) revealed that 1 (of 4096 sequences screened) DNA sequences specifically bound a 160 Kda protein over-expressed in PIN and not found in BPH, SV or PCA glands (n=11). The gene encoding for the 160 Kda protein was cloned from a lamda ZAP expression library by ‘in situ’ hybridization assays with the 32 P labeled DNA sequence. Sequencing revealed that the gene encoding for the 160 Kda protein was ABCA5, a member of the superfamily of ATP-binding cassette (ABC) transporters of multi-drug resistant genes. RT-PCR assays indicated the mRNA was over-expressed in primary PIN cell cultures and by PIN tissue, but it was not present in BPH, or SV tissue. Rabbit polyclonal antibodies were raised against a n-terminal peptide (20 b) plus a c-terminal peptide (20b) and found to specifically label the cell junctions of 3% glutaraldehyde fixed cultured cells and to label putative adult cancer stem cells in sections of PIN tissue. ‘Blinded’ ELISA studies with urine specimens from biopsed patients showed that ABCA5 was over-expressed urine from patients with PIN (n=∼20), faintly expressed in PIN + PCA patients (n=8), and not expressed in BPH (n=10) or normal patients (n=20). Conclusions: The data suggest that the expression of ABCA5 is over-expressed by PIN and is a urine diagnostic marker for detection of the disease (>95% COI). Supported by NIH-NCI grant CA90397 to mes and by GTx. [Table: see text]

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