OBJECTIVES: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in males in the United States. The mortality is due mainly to distant metastasis. Therefore, predicting the prognosis of prostate cancer patients is an important clinical problem. Previously, we demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5-phenylpentanamide] reduces experimental metastasis in animal model systems. In this study, we investigated the potential of 12-LOX as a predictor for the aggressiveness of prostate cancer. METHODS: The mRNA expression level of 12-LOX in 122 matching prostate normal and cancerous tissues were measured by quantitative reverse transcription- polymerase chain reaction. Possible association between 12-LOX expression and histologic grade, pathologic and clinical stage, margin positivity, age, and race was analyzed. RESULTS: 12-LOX mRNA levels were elevated in cancer cells and the expression associated with poor differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122 evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer tissues compared with the matching normal tissues. A statistically significantly greater number of cases were found to have an elevated level of 12-LOX among T3, high grade, and surgical margin-positive than T2, intermediate, and low grade, and surgical margin-negative prostatic adenocarcinomas. CONCLUSIONS: Our data suggest that elevation of 12-LOX mRNA expression occurs more frequently in advanced stage, high-grade prostate cancer and that 12-LOX may serve as an indicator for progression and prognosis of prostate cancer. This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents.
OBJECTIVES:Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in males in the United States. The mortality is due mainly to distant metastasis. Therefore, predicting the prognosis of prostate cancerpatients is an important clinical problem. Previously, we demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5-phenylpentanamide] reduces experimental metastasis in animal model systems. In this study, we investigated the potential of 12-LOX as a predictor for the aggressiveness of prostate cancer. METHODS: The mRNA expression level of 12-LOX in 122 matching prostate normal and cancerous tissues were measured by quantitative reverse transcription- polymerase chain reaction. Possible association between 12-LOX expression and histologic grade, pathologic and clinical stage, margin positivity, age, and race was analyzed. RESULTS:12-LOX mRNA levels were elevated in cancer cells and the expression associated with poor differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122 evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer tissues compared with the matching normal tissues. A statistically significantly greater number of cases were found to have an elevated level of 12-LOX among T3, high grade, and surgical margin-positive than T2, intermediate, and low grade, and surgical margin-negative prostatic adenocarcinomas. CONCLUSIONS: Our data suggest that elevation of 12-LOX mRNA expression occurs more frequently in advanced stage, high-grade prostate cancer and that 12-LOX may serve as an indicator for progression and prognosis of prostate cancer. This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents.
Authors: Naoko Kobayashi; R James Barnard; Susanne M Henning; David Elashoff; Srinivasa T Reddy; Pinchas Cohen; Pak Leung; Jenny Hong-Gonzalez; Stephen J Freedland; Jonathan Said; Dorina Gui; Navindra P Seeram; Laura M Popoviciu; Dilprit Bagga; David Heber; John A Glaspy; William J Aronson Journal: Clin Cancer Res Date: 2006-08-01 Impact factor: 12.531
Authors: Uddhav P Kelavkar; Wayne Glasgow; Sandra J Olson; Barbara A Foster; Scott B Shappell Journal: Neoplasia Date: 2004 Nov-Dec Impact factor: 5.715
Authors: Joshua D Deschamps; Jeffrey T Gautschi; Stephanie Whitman; Tyler A Johnson; Nadine C Gassner; Phillip Crews; Theodore R Holman Journal: Bioorg Med Chem Date: 2007-08-22 Impact factor: 3.641
Authors: Daotai Nie; Jeffrey Nemeth; Yan Qiao; Alex Zacharek; Li Li; Kenny Hanna; Keqin Tang; Gilda G Hillman; Michael L Cher; David J Grignon; Kenneth V Honn Journal: Clin Exp Metastasis Date: 2003 Impact factor: 5.150