title: Knockout of phospholipase Cε attenuates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis.
abstract: Bladder cancer frequently shows mutational activation of the oncogene Ras, which is associated with bladder carcinogenesis. However, the signaling pathway downstream of Ras remains to be fully elucidated. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) is able to induce bladder cancer by driving the clonal expansion of initiated cells carrying the activated form of Ras. Phospholipase Cε (PLCε) is the main target of BBN, while the tumor promoting role of PLCε remains controversial. The present study examined the role of PLCε in BBN‑induced bladder carcinogenesis of mice with genetically inactivated PLCε. Using light and electron microscopy, the present study demonstrated that PLCε(‑/‑) mice were resistant to BBN‑induced bladder carcinogenesis. Furthermore, it was demonstrated that cyclooxygenase 2 and vascular endothelial growth factor‑A were affected by the PLCε background of the mice, suggesting that the role of PLCε in tumor promotion may be ascribed to augmentation of inflammatory responses and angiogenesis. These results indicated that PLCε is crucial for BBN‑induced bladder carcinogenesis as well as signaling downstream of Ras, and that PLCε is a candidate molecular target for the development of anti-cancer drugs.
authors.affiliation: Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Taimao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Rehabilitation Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110036, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Hospital of Beijing Military District of People's Liberation Army, Beijing 100070, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Infection Section 15, The 302 Hospital of Chinese People's Liberation Army, Beijing 100039, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Urology, The 463 Hospital of Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002085:Butylhydroxybutylnitrosamine; D063646:Carcinogenesis / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism*; D001743:Urinary Bladder / Q000473:pathology / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D002085:Butylhydroxybutylnitrosamine; D051546:Cyclooxygenase 2; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon