Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer

Xiang Gao, David Grignon, Taibi Chbihi, Alex Zacharek, Yong Q. Chen, Wael Sakr, Arthur T. Porter, John D. Crissman, J. Edson Pontes, Isaac J. Powell, Kenneth V. Honn

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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 levels 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.

Original languageEnglish (US)
Pages (from-to)227-237
Number of pages11
JournalUrology
Volume46
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

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Arachidonate 12-Lipoxygenase
Prostatic Neoplasms
Messenger RNA
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Neoplasm Metastasis
Lipoxygenase Inhibitors
Second Primary Neoplasms
Arachidonic Acid
Reverse Transcription
Prostate
Cause of Death
Neoplasms
Adenocarcinoma
Animal Models

ASJC Scopus subject areas

  • Urology

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Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. / Gao, Xiang; Grignon, David; Chbihi, Taibi; Zacharek, Alex; Chen, Yong Q.; Sakr, Wael; Porter, Arthur T.; Crissman, John D.; Edson Pontes, J.; Powell, Isaac J.; Honn, Kenneth V.

In: Urology, Vol. 46, No. 2, 1995, p. 227-237.

Research output: Contribution to journalArticle

Gao, X, Grignon, D, Chbihi, T, Zacharek, A, Chen, YQ, Sakr, W, Porter, AT, Crissman, JD, Edson Pontes, J, Powell, IJ & Honn, KV 1995, 'Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer', Urology, vol. 46, no. 2, pp. 227-237. https://doi.org/10.1016/S0090-4295(99)80198-8
Gao, Xiang ; Grignon, David ; Chbihi, Taibi ; Zacharek, Alex ; Chen, Yong Q. ; Sakr, Wael ; Porter, Arthur T. ; Crissman, John D. ; Edson Pontes, J. ; Powell, Isaac J. ; Honn, Kenneth V. / Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. In: Urology. 1995 ; Vol. 46, No. 2. pp. 227-237.
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abstract = "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 levels 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.",
author = "Xiang Gao and David Grignon and Taibi Chbihi and Alex Zacharek and Chen, {Yong Q.} and Wael Sakr and Porter, {Arthur T.} and Crissman, {John D.} and {Edson Pontes}, J. and Powell, {Isaac J.} and Honn, {Kenneth V.}",
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T1 - Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer

AU - Gao, Xiang

AU - Grignon, David

AU - Chbihi, Taibi

AU - Zacharek, Alex

AU - Chen, Yong Q.

AU - Sakr, Wael

AU - Porter, Arthur T.

AU - Crissman, John D.

AU - Edson Pontes, J.

AU - Powell, Isaac J.

AU - Honn, Kenneth V.

PY - 1995

Y1 - 1995

N2 - 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 levels 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.

AB - 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 levels 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.

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