Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen.

TLDR

A novel 100,000‑Da prostate‑specific membrane glycoprotein (PSM) has been identified by the monoclonal antibody 7E11‑C5 and is expressed exclusively in normal and malignant prostate cells and metastases. The study aims to report the molecular cloning of a full‑length 2.65‑kb cDNA encoding the PSM antigen. The cDNA was isolated from a human LNCaP library using PCR with degenerate primers. Sequence analysis revealed a 54% homology to transferrin receptor mRNA between nucleotides 1250–1700, a predicted transmembrane domain delineating intra‑ and extracellular regions, and suggested that, unlike secreted PSA and PAP, PSM’s integral membrane nature could make it a viable target for imaging and cytotoxic therapies.

Abstract

Recently, a novel M(r) 100,000 prostate-specific membrane glycoprotein (PSM) has been detected by the prostate-specific monoclonal antibody 7E11-C5, raised against the human prostatic carcinoma cell line LNCaP. The PSM antigen is expressed exclusively by normal and neoplastic prostate cells and metastases. We now report the molecular cloning of a full-length 2.65-kilobase complementary DNA encoding the PSM antigen from a human LNCaP complementary DNA library by polymerase chain reaction using degenerate oligonucleotide primers. Analysis of the complementary DNA sequence has revealed that a portion of the coding region, from nucleotide 1250 to 1700, has 54% homology to the human transferrin receptor mRNA. The deduced polypeptide has a putative transmembrane domain enabling the delineation of intra- and extracellular portions of this antigen. In contrast to prostate-specific antigen and prostatic acid phosphatase which are secreted proteins, PSM as an integral membrane protein may prove to be effective as a target for imaging and cytotoxic targeting modalities.