Abstract
Rapid expression cloning and differential RNA display identifies a gene, named prostate tumor inducing gene-1 (PTI-1), that is differentially expressed in prostate cancer versus normal prostate and benign prostatic hypertrophy. PTI-1 encodes a truncated and mutated human elongation factor 1α, and its 5′ untranslated region (UTR) shares significant homology with the 23S rRNA gene of Mycoplasma hyopneumoniae. PCR with human genomic DNAs, using PTI-1 5′ UTR-specific primers, suggests that this sequence is part of the human genome. Furthermore, reverse transcription (RT)-PCR, with one primer specific to the 5′ UTR region and the other to the elongation factor 1α coding region, amplifies PTI-1 transcripts from total RNA of various human tumor cell lines and blood samples from prostate carcinoma patients. RT-PCR products with the predicted size and sequence of PTI-1 are detected in RNAs from cell lines of human prostate, breast, and colon carcinomas. This RT-PCR product is shown by Southern blotting and sequence analyses to contain the junction sequence between the 5′ UTR and the coding region of the PTI-1 gene. Furthermore, RT-PCR analysis indicates that the PTI-1 gene is also expressed in prostate carcinoma patient-derived blood samples. On the basis of serial dilution experiments, PTI-1 can detect 1 prostate carcinoma cell in 108 cells not expressing PTI-1. In this context, PTI-1 represents a sensitive marker for detecting human prostate cancer in the bloodstream. This study confirms the authenticity of the PTI-1 gene and documents its potential clinical utility as a sensitive and specific indicator of prostate cancer progression.
This work was supported by an award from the Association for the Cure of Cancer of the Prostate; the Samuel Waxman Cancer Foundation; and the Chernow Endowment. P. B. F. is a Chernow Research Scientist in the Departments of Pathology and Urology.