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Alternatively Spliced Variants of Prostate-specific Membrane Antigen RNA: Ratio of Expression as a Potential Measurement of Progression¹

Urology Service, Department of Surgery and the George M. O'Brien Urology Research Center for Prostate Cancer, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotides 114–380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9–11, carcinoma of the prostate from 3–6, benign prostatic hypertrophy from 0.75–1.6, and normal prostate from 0.075–0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression.

¹ This work was supported in part by NIH Grants DK-CA 47650. I-P. H. was the recipient of an American Foundation for Urologic Diseases Research Fellowship. Partial support was also provided by CaPCure and the Koch Foundation.

² To whom requests for reprints should be addressed, at George M. O'Brien Urology Research Center for Prostate Cancer, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 1/17/95. Accepted 2/27/95.

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