Objectives: Determining the genetic changes associated with the development of metastatic prostate cancer is of utmost importance in patient prognosis and therapy. Our goal is to identify genes whose enhanced expression is associated with metastatic prostate cancer.
Methods: Total ribonucleic acid was isolated from prostatic tissue exhibiting no histologic evidence of carcinoma and from a prostatic adenocarcinoma lymph node metastasis. The differential display polymerase chain reaction (DD-PCR) technique was used to isolate genes that exhibited increased expression in the metastatic tissue sample. Isolated PCR products were cloned, sequenced, and identified by screening complementary deoxyribonucleic acid (cDNA) databases.
Results: Using DD-PCR, we identified three cDNA clones that exhibit enhanced expression in metastatic prostatic tissue. Two of these cDNA clones have not been identified because they show no homology to known database sequences. The third cDNA is 166 base pairs in length and exhibits 93% homology to nucleotides 662 to 828 of human macrophage migration inhibitory factor (MIF). Slot blot analysis using RNA from various prostate-derived sources suggests that increased expression of MIF is associated with metastatic prostate cancer.
Conclusions: These results show that the DD-PCR technique is applicable for the identification and cloning of human genes that exhibit enhanced expression in prostate cancer metastases. These results indicate the possibility that MIF production by prostate cancer cells plays a role in the development of metastases. The enhanced expression of MIF by prostate cancer cells may be a potential prognostic marker for metastatic prostate cancer.