Human 5-, 12- and 15-lipoxygenase-1 coexist in kidney but show opposite trends and their balance changes in cancer

Gohara,Amira; Eltaki,Noha; Sabry,Dina; Murtagh ,Daniel; Jankun,Jerzy; Selman,Steven H.; Skrzypczak-Jankun,Ewa

doi:10.3892/or.2012.1924

Human 5-, 12- and 15-lipoxygenase-1 coexist in kidney but show opposite trends and their balance changes in cancer

Authors:
- Amira Gohara
- Noha Eltaki
- Dina Sabry
- Daniel Murtagh
- Jerzy Jankun
- Steven H. Selman
- Ewa Skrzypczak-Jankun
View Affiliations

Affiliations: Department of Pathology, College of Medicine, University of Toledo, Toledo, OH 43614, USA, Department of Urology, College of Medicine, University of Toledo, Toledo, OH 43614, USA
Published online on: July 20, 2012 https://doi.org/10.3892/or.2012.1924
Pages: 1275-1282

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lipoxygenases make an impact on every stage of cancer affecting carcinogenesis, metastasis and apoptosis. While there is a rich literature on individual lipoxygenases we lack extensive data on their coexistence and balance in different organs and types of cancer. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, characterized by a lack of early warning signs, diverse clinical manifestations, resistance to radiation and chemotherapy. One third of patients will relapse and the 5‑year survival rate is <10% in cases of metastases. Many drugs are metabolized in the kidneys and might interact with lipoxygenases that are biocatalysts for many endo- and xenobiotics. In the present study, we examined the kidney tissue from healthy individuals and cancer patients by immunohistochemical analysis for the presence of 3 lipoxygenases: 5-LOX, 12S-LOX and 15-LOX-1. Our findings confirmed their coexistence and opposite trends of manifestation in the course of disease with increased 15-LOX-1 and decreased 5- and 12-LOX levels at the onset of cancer reversing with the progressing stage of the disease or the grade of tumor. Unlike other malignancies, there are no biomarkers to individualize RCC management. Modern therapies are using TKI therapy, targeting VEGF and may cause hypertension as a side-effect. 12S-LOX is intertwined with kinases and VEGF and increased secretion of 12S-HETE in urine is known to accompany hypertension. Thus, it may be valuable to probe 12S-LOX activity and monitor its natural metabolite to seek a possible aid in directing the treatment of patients.

View Figures

View References

1	Chow WH, Dong L and Devesa S: Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 7:245–257. 2010. View Article : Google Scholar : PubMed/NCBI
2	American Cancer Society. Cancer Facts and Figures 2011. American Cancer Society; Atlanta: 2011
3	Heng DY, Xie W, Bjarnason GA, et al: Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy. Cancer. 117:2637–2642. 2011. View Article : Google Scholar : PubMed/NCBI
4	Berglund L, Björling E, Oksvold P, et al: A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol Cell Proteomics. 7:2019–2027. 2008. View Article : Google Scholar : PubMed/NCBI
5	Rhodes DR, Kalyana-Sundaram S, Mahavisno V, et al: Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 9:166–180. 2007. View Article : Google Scholar : PubMed/NCBI
6	Pontén F, Jirström K and Uhlen M: The Human Protein Atlas - a tool for pathology. J Pathol. 216:387–393. 2008.
7	Haeggström JZ and Funk CD: Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease. Chem Rev. 111:5866–5898. 2011.PubMed/NCBI
8	Skrzypczak-Jankun E, Chorostowska-Wynimko J, Selman SH and Jankun J: Lipoxygenases - a challenging problem in enzyme inhibition and drug development. Curr Enzym Inhib. 3:119–132. 2007. View Article : Google Scholar
9	Kulkarni AP: Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics. Cell Mol Life Sci. 58:1805–1825. 2001. View Article : Google Scholar : PubMed/NCBI
10	Fleming ID, Cooper JS, Henson DE, et al: AJCC Cancer Staging Manual. Lippincott-Raven; Philadelphia: 1997
11	Sibony M and Vieillefond A: Non-clear cell renal cell carcinoma. 2008 update in renal tumor pathology. Ann Pathol. 28:381–401. 2008.(In French).
12	Wang D and Dubois RN: Eicosanoids and cancer. Nat Rev Cancer. 10:181–193. 2010. View Article : Google Scholar
13	Faronato M, Muzzonigro G, Milanese G, et al: Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma. Histol Histopathol. 22:1109–1118. 2007.PubMed/NCBI
14	Matsuyama M, Yoshimura R, Mitsuhashi M, et al: 5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway. Oncol Rep. 14:73–79. 2005.PubMed/NCBI
15	Yoshimura R, Inoue K, Kawahito Y, et al: Expression of 12-lipoxygenase in human renal cell carcinoma and growth prevention by its inhibitor. Int J Mol Med. 13:41–46. 2004.PubMed/NCBI
16	Philips BJ, Dhir R, Hutzley J, Sen M and Kelavkar UP: Polyunsaturated fatty acid metabolizing 15-Lipoxygenase-1 (15-LO-1) expression in normal and tumorigenic human bladder tissues. Appl Immunohistochem Mol Morphol. 16:159–164. 2008. View Article : Google Scholar : PubMed/NCBI
17	Jack GS, Brash AR, Olson SJ, et al: Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation with grade and expression in high-grade prostatic intraepithelial neoplasia. Hum Pathol. 31:1146–1154. 2000. View Article : Google Scholar : PubMed/NCBI
18	Jiang WG, Douglas-Jones A and Mansel RE: Levels of expression of lipoxygenases and cyclooxygenase-2 in human breast cancer. Prostaglandins Leukot Essent Fatty Acids. 69:275–281. 2003. View Article : Google Scholar : PubMed/NCBI
19	Yoshimura R, Matsuyama M, Tsuchida K, Kawahito Y, Sano H and Nakatani T: Expression of lipoxygenase in human bladder carcinoma and growth inhibition by its inhibitors. J Urol. 170:1994–1999. 2003. View Article : Google Scholar : PubMed/NCBI
20	Brown HA and Marnett LJ: Introduction to lipid biochemistry, metabolism, and signaling. Chem Rev. 111:5817–6512. 2011. View Article : Google Scholar : PubMed/NCBI
21	Rini BI, Cohen DP, Lu DR, et al: Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 103:763–773. 2011. View Article : Google Scholar
22	González-Núñez D, Claria J, Rivera F and Poch E: Increased levels of 12(S)-HETE in patients with essential hypertension. Hypertension. 37:334–338. 2001.PubMed/NCBI