Effects of different forms of prostate specific antigen on prostate cancer cell invasion / by Andrew Philip Cumming
Cumming, Andrew Philip
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"Prostate cancer (PCa) is one of the most common cancers in males around the world. Prostate-specific antigen (PSA) is a serine protease that is secreted at high levels by prostate epithelial cells and most prostate cancer cells. It is thought that this enzyme is involved in prostate cancer cell invasion. This study aimed to test the effects of enzymatically active PSA and inactive forms of PSA on prostate cancer cell invasion. PSA is transcribed with a 17 amino acid secretory "pre" sequence and a 7 amino acid latency-conferring "pro" sequence. A deletion mutant lacking the "pro" region of the full-length preproPSA gene was used to create the prePSA gene, in the hopes that enzymatically active PSA would be formed upon cleavage of the "pre" sequence. Full length preproPSA cDNA and prePSA cDNA were each inserted into plasmids that allowed for inducible expression of the PSA genes under the control of the insect hormone derivative, ponasterone A (PonA). DU-145 subclones were created with the ability to inducibly produce preproPSA (DU-pERV3 C3 ppPSA) and prePSA (DU-pERV3 C3 prePSA).