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A Novel Form of Prostate-specific Antigen Transcript Produced by Alternative Splicing¹

Department of Urology [T. T., T. Yo., T. Yu., Y. O.] and Central Research Laboratory [T. I.], Shiga University of Medical Science, Shiga 520-2192, Japan

Molecular characterization of prostate-specific antigen (PSA) has not been well elucidated, despite a great deal of clinical study. We examined the heterogeneity of PSA using reverse transcription-PCR and direct sequencing. A novel, alternatively spliced variant of the PSA transcript was found in prostate cancer (PC), as well as in benign prostatic tissue. This alternative splicing leads to the deletion of 44 amino acid residues (amino acids 45–88) from mature PSA, resulting in the loss of asparagine 45, which is a binding site for a carbohydrate chain. By these nested reverse transcription-PCR systems, this novel, alternatively spliced PSA gene was recognized in 13 of 18 (72.2%) cases with noncancerous prostate tissue, 4 of 5 (80.0%) PC cases, and 3 of 12 (25.0%) blood samples from PC patients (noncancerous prostate tissue group versus blood sample group, P = 0.011). At present, the biological significance of this alternative splicing remains to be established.

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