Cloning and characterization of the α1-antichymotrypsin produced by human prostate tissue

Abstract

BACKGROUND α1‐antichymotrypsin (ACT) forms stable complexes with prostate‐specific antigen (PSA), a serine protease, and this complex is the major form of PSA in the blood circulation. α1‐antichymotrypsin occurs in the blood in approximately 105 molar excess to PSA, mainly due to hepatic production, but local prostatic production of ACT has been demonstrated by immunohistochemistry and in situ hybridization. The present study was performed to further characterize this prostate‐produced ACT. METHODS The nucleotide structure of the prostatic transcript was determined from ACT coding clones isolated from prostatic cDNA. The occurrence of a prostatic ACT transcript was analyzed by Northern blot. RT‐PCR was used to detect ACT transcripts in cultured prostatic cancer cells. RESULTS Screening of two prostatic cDNA libraries showed the frequency of ACT transcripts to be about 1 clone in 40,000. The cDNA sequence of prostatic ACT is identical to that of the previously published hepatic ACT. Northern blot analysis of mRNA extracted from prostatic tissue showed a single transcript of approximately 1.5 kb. RT‐PCR analysis demonstrated an ACT transcript in cultured prostatic cancer cells. CONCLUSIONS In this study we provide further evidence for a local, prostatic production of ACT. The cDNA sequence data suggest that the peptide backbone of prostatic ACT is identical to the protein derived from the liver, and thus may be functional as a protease inhibitor. Prostate 34:155–161, 1998.© 1998 Wiley‐Liss, Inc.

Distribution and secretory pathways of prostate specific antigen, α1‐antichymotrypsin and prostate secretory granules in prostate cancers

“…Wu et al . reported, from their analysis of cDNA sequence data, that the peptide backbone of prostatic ACT is identical to the protein derived from the liver, and thus may be functional as a protease inhibitor 22 . From our findings, ACT is mainly seen in normal duct and cancer cells.…”

The role of prostate‐specific antigen in the clinical evaluation of prostatic disease

“…4). ACT appears to be produced in small amounts in normal and BPH tissue, and in much higher amounts by prostate cancer cells [37–40]. In addition, Miller et al.…”

Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA and alpha-1-antichymotrypsin in prostatic tissue sections

“…31 In blood, ACT is the predominant inhibitor of PSA and approximately 80% of serum-PSA is usually bound to ACT. However, there is a difference in the degree of complex formation in patients with either CAP or BPH, which has been used to increase the speci®city of PSA as an indicator for CAP.…”