Knockout of phospholipase CŒµ attenuates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis
Authors: Chuize Kong
Taimao Jiang
Lin Li
Dongye Liu
Zhijun Yang
Tao Liu
Yunfeng Bai
Journal: Molecular Medicine Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Bladder cancer; Ras; BBN; PLCŒµ; carcinogenesis
Affiliations: Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China., Department of Rehabilitation Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110036, P.R. China., Department of Neurosurgery, Hospital of Beijing Military District of People's Liberation Army, Beijing 100070, P.R. China., Infection Section 15, The 302 Hospital of Chinese People's Liberation Army, Beijing 100039, P.R. China., Department of Urology, The 463 Hospital of Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China.

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 CŒµ (PLCŒµ) is the main target of BBN, while the tumor promoting role of PLCŒµ remains controversial. The present study examined the role of PLCŒµ in BBN‚Äëinduced bladder carcinogenesis of mice with genetically inactivated PLCŒµ. Using light and electron microscopy, the present study demonstrated that PLCŒµ(‚Ä?‚Ä? mice were resistant to BBN‚Äëinduced bladder carcinogenesis. Furthermore, it was demonstrated that cyclooxygenase 2 and vascular endothelial growth factor‚ÄëA were affected by the PLCŒµ background of the mice, suggesting that the role of PLCŒµ in tumor promotion may be ascribed to augmentation of inflammatory responses and angiogenesis. These results indicated that PLCŒµ is crucial for BBN‚Äëinduced bladder carcinogenesis as well as signaling downstream of Ras, and that PLCŒµ is a candidate molecular target for the development of anti-cancer drugs. 

Retracted: No

PubPeer comments:
 Figure 5 u2013 possible duplication in AKT bands in a different set of animals according the figure legends. Could authors check it please?  , 
 Dear Chrysotoxum Bicinctum, I am first author on this manuscript, and I have consulted the high-resolution scans of the original Western blots used to generate the Western blots in this figure. You have correctly identified an error which was introduced during final figure assembly. As shown in the scan below, we incorrectly utilized the total AKT band outlined in red in both panels A and C. The red-outlined total AKT band should have been utilized only in Figure 5C, while (the virtually identical) total AKT band outlined in blue should have been utilized in panel 5A.  We apologize for the error, and thank you for alerting us. We provide a corrected figure below, and I and Dr. Gruppuso will followup with the journal. best, Dudley  , 
 12 November 2020 Correction for u201cHepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2),u201d by Dudley W. Lamming, Gokhan Demirkan, Joan M. Boylan, Maria M. Mihaylova, Tao Peng Jonathan Ferreira, Nicola Neretti, Arthur Salomon, David M. Sabatini, and Philip A. Gruppuso, which was first published September 26, 2013; 10.1096 fj.13u2010237743 (FASEB J. 28, 300u2013315). The authors note that there is an error in Figure 5A. The total AKT band in Figure 5C was erroneously duplicated in Figure 5A during the final figure assembly. This error does not affect any of the conclusions presented in the article. https: faseb.onlinelibrary.wiley.com doi 10.1096 fsb2.21165 ,