Polyunsaturated Fatty Acid Metabolizing 15-Lipoxygenase-1 (15-LO-1) Expression in Normal and Tumorigenic Human Bladder Tissues

Abstract

Diets high in fat seem to correspond with an increased risk of certain forms of cancer, including bladder BlCa. This preliminary study examined the expression and enzyme activity profile of the polyunsaturated fatty acid metabolizing enzyme 15-Lipoxygenase-1 (15-LO-1) in human tissues from normal bladder and bladder tumors (stages CIS-T3/T4). Human tissue samples from normal (donor) bladder and bladder tumors (stages CIS-T3/T4; non-Bacillus Calmette-Guerin-treated) were grossly microdissected and analyzed for 15-LO-1 protein expression [immunohistochemistry (IHC)/Western blot], mRNA expression (quantitative real-time polymerase chain reaction) and enzyme activity profiles. Our results demonstrated that 15-LO-1 expression (protein/mRNA) and enzyme activity varied with BlCa progression. Specifically, IHC analyses of 15-LO-1 protein levels revealed decreased expression with increased bladder tumor stage. In particular, a statistically significant decrease in 15-LO-1 expression in stage T3/T4 bladder tumors compared with normal tissues (P<0.001) was observed. In agreement with IHC results, Western blot, quantitative real-time polymerase chain reaction, and enzymatic activity analyses demonstrated increased 15-LO-1 protein, mRNA, and enzyme activity, respectively, in normal human bladder tissues in comparison with stage T3/T4 human bladder tumors. Our finding of variable 15-LO-1 expression and enzyme activity in bladder tissues suggests a role for 15-LO-1 in bladder carcinogenesis.

Enzyme 15‐lipoxygenase 1 promotes hypoxia‐inducible factor 1α turnover and reduces vascular endothelial growth factor expression: implications for angiogenesis

“…Both anticarcinogenic and procarcinogenic roles have been proposed . In agreement with its tumor suppressor function, 15‐LO1 is downregulated in many human cancer types in comparison with their benign counterparts , whereas it is overexpressed in prostate cancer and its precursors . Similarly to its role in colorectal carcinogenesis , 15‐LO1 appears to function as a tumor suppressor in many other organ systems.…”

Effects of costimulation on intrahepatic immunopathogenesis in patients with chronic HBV infection

“…However, immunohistochemical pathologists, such as Becker and Taylor [28], believe that immunohistochemistry-based methods retain morphological data but prove difficult to quantify, and that Western blotting may be used for quantitative detection of protein in tissue. In a study by Philips et al, both Western blotting and immunohistochemistry were used to investigate enzyme proteins in the human bladder [29]. According to Becker’s strategy and Phillips’ measurements, we applied two techniques, immunohistochemistry and Western blotting, to explore the effects of costimulatory proteins in liver.…”

ALOX15 as a suppressor of inflammation and cancer: Lost in the link

“…In contrast, other LOXs do not appear to be significantly altered during colonic tumorigenesis [31, 73, 74]. Downregulation of ALOX15 expression has also been reported in various other human cancers, including lung [75], esophageal [76], breast [77], endometrial [78], urinary bladder [79] and pancreatic cancer [80]. Additionally, screening of 128 different human cancer cell lines representing 20 different human cancers, including all common human cancers, showed that ALOX15 expression was markedly repressed [75].…”