Objective: The objective of this study was to investigate the significance of the activated Akt-mammalian target of rapamycin (Akt-mTOR) signaling pathway in the progression of prostate cancer. Materials and Methods: The expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in 175 prostate specimens, including 61 normal prostate tissues as a control, 24 high-grade prostatic intraepithelial neoplasias (HGPINs) and 90 clinically localized prostate cancers, were evaluated by immunohistochemical staining. p-Akt and p-mTOR ratios, which were defined as the expression level of p-Akt in relation to that of Akt and the expression level of p-mTOR in relation to that of mTOR, respectively, in these specimens were calculated. Results: Expression levels of all four molecules, including Akt, p-Akt, mTOR and p-mTOR, were significantly greater in the HGPIN group compared with the normal control and prostate cancer groups. Furthermore, the p-Akt ratio in the prostate cancer group was significantly lower than that in the HGPIN group, while there was no significant difference in the p-mTOR ratio between the HGPIN and prostate cancer groups. In the prostate cancer group, no significant relationships were observed between major clinicopathological parameters and the expression levels as well as the ratios of p-Akt or p-mTOR. Conclusions: The Akt-mTOR signaling pathway may play a limited role in the progression of prostate cancer.

1.
Sheppard K, Kinross KM, Solomon B, Pearson RB, Phillips WA: Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog 2012;17:69-95.
2.
Mahajan K, Mahajan NP: PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics. J Cell Physiol 2012;227:3178-3184.
3.
Fasolo A, Sessa C: Targeting mTOR pathways in human malignancies. Curr Pharm Des 2012;18:2766-2777.
4.
Markman B, Dienstmann R, Tabernero J: Targeting the PI3K/Akt/mTOR pathway - beyond rapalogs. Oncotarget 2010;1:530-543.
5.
Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL: Integrative genomic profiling of human prostate cancer. Cancer Cell 2010;18:11-22.
6.
Shimizu Y, Segawa T, Inoue T, Shiraishi T, Yoshida T, Toda Y, Yamada T, Kinukawa N, Terada N, Kobayashi T, Kinoshita H, Kamoto T, Nakamura E, Ogawa O: Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men. BJU Int 2007;100:685-690.
7.
Oh MH, Lee HJ, Yoo SB, Xu X, Choi JS, Kim YH, Lee SY, Lee CT, Jheon S, Chung JH: Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer. Virchows Arch 2012;460:601-609.
8.
Sun CH, Chang YH, Pan CC: Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder. Histopathology 2011;58:1054-1063.
9.
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005;29:1228-1242.
10.
Kurahashi T, Miyake H, Hara I, Fujisawa M: Expression of major heat shock proteins in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. J Urol 2007;177:757-761.
11.
Kreisberg JI, Malik SN, Prihoda TJ, Bedolla RG, Troyer DA, Kreisberg S, Ghosh PM: Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Res 2004;64:5232-5236.
12.
Dai B, Kong YY, Ye DW, Ma CG, Zhou X, Yao XD: Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics. BJU Int 2009;104:1009-1016.
13.
Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W, Sobue T: Cancer incidence and incidence rates in Japan in 2005: based on data from 12 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 2011;41:139-147.
14.
So A, Gleave M, Hurtado-Col A, Nelson C: Mechanisms of the development of androgen independence in prostate cancer. World J Urol 2005;23:1-9.
15.
Kasper S, Cookson MS: Mechanisms leading to the development of hormone-resistant prostate cancer. Urol Clin North Am 2006;33:201-210.
16.
Morgan TM, Koreckij TD, Corey E: Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets 2009;9:237-249.
17.
Evren S, Dermen A, Lockwood G, Fleshner N, Sweet J: mTOR-RAPTOR and 14-3-3σ immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study. J Clin Pathol 2011;64:683-688.
18.
Brown RE, Zotalis G, Zhang PL, Zhao B: Morphoproteomic confirmation of a constitutively activated mTOR pathway in high grade prostatic intraepithelial neoplasia and prostate cancer. Int J Clin Exp Pathol 2008;1:333-342.
19.
Kinkade CW, Castillo-Martin M, Puzio-Kuter A, Yan J, Foster TH, Gao H, Sun Y, Ouyang X, Gerald WL, Cordon-Cardo C, Abate-Shen C: Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model. J Clin Invest 2008;118:3051-3064.
20.
Kruck S, Bedke J, Hennenlotter J, Ohneseit PA, Kuehs U, Senger E, Sievert KD, Stenzl A: Activation of mTOR in renal cell carcinoma is due to increased phosphorylation rather than protein overexpression. Oncol Rep 2010;23:159-163.
21.
Jendrossek V, Henkel M, Hennenlotter J, Vogel U, Ganswindt U, Müller I, Handrick R, Anastasiadis AG, Kuczyk M, Stenzl A, Belka C: Analysis of complex protein kinase B signalling pathways in human prostate cancer samples. BJU Int 2008;102:371-382.
22.
Xia SJ, Cui D, Jiang Q: An overview of prostate diseases and their characteristics specific to Asian men. Asian J Androl 2012;14:458-464.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.