Immunohistochemical expression of mTOR negatively correlates with PTEN expression in gastric carcinoma

Li,Min; Sun,Huawen; Song,Lujun; Gao,Xiaodong; Chang,Wenju; Qin,Xinyu

doi:10.3892/ol.2012.930

Immunohistochemical expression of mTOR negatively correlates with PTEN expression in gastric carcinoma

Authors:
- Min Li
- Huawen Sun
- Lujun Song
- Xiaodong Gao
- Wenju Chang
- Xinyu Qin
View Affiliations

Affiliations: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
Published online on: September 21, 2012 https://doi.org/10.3892/ol.2012.930
Pages: 1213-1218

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

The phosphoinositide‑3 kinase (PI3K)‑AKT-mammalian target of rapamycin (mTOR) pathway is a cellular pathway involved in cell growth, tumorigenesis and cell invasion which is frequently activated in various types of cancer. The downstream effector of the pathway is mTOR which is important in cellular growth and homeostasis and aberrant activation of mTOR has been reported in several types of cancer. The tumor suppressor gene phosphatase and tensin homolog (PTEN) is essential in this pathway for inhibiting tumor invasion and metastasis. However, the involvement of mTOR and PTEN in the progression of human gastric cancer remains to be identified. Immunohistochemical staining was performed to detect the expression of mTOR and PTEN in paraffin‑embedded gastric tissue sections obtained from 33 patients with gastric cancer and 30 normal controls. The expressed mTOR was mainly distributed in the cytoplasm, while PTEN was mainly localized to the nucleus. By considering negative mTOR expression with positive PTEN expression as one group and negative PTEN expression with positive mTOR expression as the other, significant statistical differences were observed in various categories, including histological types and metastatic and clinical pathology stages, between the 2 groups (P<0.01 or 0.05). The results indicated that the expression levels of mTOR and PTEN were negatively correlated in the PI3K‑AKT‑mTOR signaling pathway. Combined detection of mTOR and PTEN expression may be used to evaluate the degree of malignancy in gastric cancer and may be a useful marker for the early diagnosis of gastric cancer.

View Figures

View References

1.	K Washington7th edition of the AJCC cancer staging manual: stomachAnn Surg Oncol1730773079201010.1245/s10434-010-1362-z20882416
2.	S LiangL HeX ZhaoMicroRNA let-7f inhibits tumor invasion and metastasis by targeting myh9 in human gastric cancerPloS One6e18409201110.1371/journal.pone.001840921533124
3.	DH RoukosTargeting gastric cancer with trastuzumab: new clinical practice and innovative developments to overcome resistanceAnn Surg Oncol171417201010.1245/s10434-009-0766-019841980
4.	N BalNE KocerME ErtorerET CanpolatF KayaselcukMaspin, E-selectin, and P-selectin expressions in papillary thyroid carcinomas and their correlation with prognostic parametersPathol Res Pract204743750200810.1016/j.prp.2008.04.01618597952
5.	X ChenJ LiaoY LuX DuanW SunActivation of the PI3K Akt pathway mediates bone morphogenetic protein 2-induced invasion of pancreatic cancer cells Panc-1Pathol Oncol Res17257261201110.1007/s12253-010-9307-120848249
6.	Z XuY ZhangJ JiangEpidermal growth factor induces HCCR expression via PI3K/Akt/mTOR signaling in PANC-1 pancreatic cancer cellsBMC Cancer10161201010.1186/1471-2407-10-16120423485
7.	AP BhattPM BhendeSH SinD RoyDP DittmerB DamaniaDual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomasBlood11544554463201010.1182/blood-2009-10-25108220299510
8.	M SajiMD RingelThe PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumorsMol Cell Endocrinol3212028201010.1016/j.mce.2009.10.01619897009
9.	S VignotS FaivreD AguirreE RaymondmTOR-targeted therapy of cancer with rapamycin derivativesAnn Oncol16525537200510.1093/annonc/mdi11315728109
10.	D MahalingamK SankhalaA MitaFJ GilesMM MitaTargeting the mTOR pathway using deforolimus in cancer therapyFuture Oncol5291303200910.2217/fon.09.919374536
11.	CB ChingDE HanselExpanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathwayLab Invest9014061414201010.1038/labinvest.2010.13320661228
12.	JS CarewKR KellyST NawrockiMechanisms of mTOR inhibitor resistance in cancer therapyTarget Oncol61727201110.1007/s11523-011-0167-821547705
13.	A YoshimiS GoyamaN Watanabe-OkochiEvi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteinsBlood11736173628201110.1182/blood-2009-12-26160221289308
14.	M MireutaA DarnelM PollakIGFBP-2 expression in MCF-7 cells is regulated by the PI3K/AKT/mTOR pathway through Sp1-induced increase in transcriptionGrowth Factors28243255201010.3109/0897719100374547220370577
15.	C LiuJL WuK XuNeuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathwayJ Neurochem11215001512201010.1111/j.1471-4159.2009.06561.x20050973
16.	SR HamiltonLA AaltonenPathology and Genetics of Tumors of the Digestive SystemWHO PressGeneva2000
17.	SB EdgeDR ByrdCC ComptonAG FritzF GreeneA TrottiAJCC cancer staging manual7th editionSpringerNew York2010
18.	X HeQ WeiX ZhangImmunohistochemical expression of CXCR4 in thyroid carcinomas and thyroid benign lesionsPathol Res Pract206712715201010.1016/j.prp.2010.05.00320646838
19.	HY NiuJH WangH LiP HeRapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cellsJ Exp Clin Canc Res3028201110.1186/1756-9966-30-2821392382
20.	M ChenJ GuGL DelclosGenetic variations of the PI3KAKT-mTOR pathway and clinical outcome in muscle invasive and metastatic bladder cancer patientsCarcinogenesis3113871391201010.1093/carcin/bgq11020530239
21.	M LiL SongX QinGlycan changes: cancer metastasis and anti-cancer vaccinesJ Biosci35665673201010.1007/s12038-010-0073-821289447
22.	F SahinR KannangaiO AdegbolaJZ WangG SuM TorbensonmTOR and P70 S6 kinase expression in primary liver neoplasmsClin Cancer Res1084218425200410.1158/1078-0432.CCR-04-094115623621
23.	K SchmidZ Bago-HorvathW BergerDual inhibition of EGFR and mTOR pathways in small cell lung cancerBr J Cancer103622628201010.1038/sj.bjc.660576120683448
24.	K HirashimaY BabaM WatanabePhosphorylated mTOR expression is associated with poor prognosis for patients with esophageal squamous cell carcinomaAnn Surg Oncol1724862493201010.1245/s10434-010-1040-120339946
25.	G YuJ WangY ChenOverexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of Chinese patients with gastric cancerClin Cancer Res1518211829200910.1158/1078-0432.CCR-08-213819223493
26.	J AnH JeongY LeeSU WooJH SeoA KimPhosphorylated Akt and phosphorylated mTOR expression in breast invasive carcinomas: analysis of 530 casesJ Breast Cancer13337348201010.4048/jbc.2010.13.4.337
27.	S BoseS ChandranJM MirochaN BoseThe Akt pathway in human breast cancer: a tissue-array-based analysisMod Pathol19238245200610.1038/modpathol.3800525
28.	RJ MotzerB EscudierS OudardEfficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trialLancet372449456200810.1016/S0140-6736(08)61039-918653228
29.	M MarinovA ZiogasOE PardoAKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001Clin Cancer Res1512771287200910.1158/1078-0432.CCR-08-216619228731
30.	KH TamZF YangCK LauCT LamRW PangRT PoonInhibition of mTOR enhances chemosensitivity in hepatocellular carcinomaCancer Lett273201209200910.1016/j.canlet.2008.08.01818824293
31.	KS JangYS SongSH JangClinicopathological significance of nuclear PTEN expression in colorectal adenocarcinomaHistopathology56229239201010.1111/j.1365-2559.2009.03468.x20102402
32.	T AndjelkovicJ BankovicJ StojsicCoalterations of p53 and PTEN tumor suppressor genes in non-small cell lung carcinoma patientsTransl Res1571928201110.1016/j.trsl.2010.09.00421146147
33.	AM Gonzalez-AnguloJ Ferrer-LozanoK Stemke-HalePI3K pathway mutations and PTEN levels in primary and metastatic breast cancerMol Cancer Ther1010931101201110.1158/1535-7163.MCT-10-108921490305
34.	DJ MulhollandLM TranY LiCell autonomous role of PTEN in regulating castration-resistant prostate cancer growthCancer Cell19792804201110.1016/j.ccr.2011.05.00621620777
35.	G HouZ LuM LiuH LiuL XueMutational analysis of the PTEN gene and its effects in esophageal squamous cell carcinomaDig Dis Sci5613151322201110.1007/s10620-010-1474-021116717
36.	MJ LangloisS BergeronG BernatchezThe PTEN phosphatase controls intestinal epithelial cell polarity and barrier function: role in colorectal cancer progressionPloS One5e15742201010.1371/journal.pone.001574221203412
37.	XH LiHC ZhengH TakahashiS MasudaXH YangY TakanoPTEN expression and mutation in colorectal carcinomasOncol Rep22757764200919724853
38.	CY GuoXF XuJY WuSF LiuPCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its significance in human gastric cancerWorld J Gastroenterol1438043811200810.3748/wjg.14.380418609703
39.	M LiL SongX GaoW ChangX QinToll-like receptor 4 on islet β cells senses expression changes in high-mobility group box 1 and contributes to the initiation of type 1 diabetesExp Mol Med442602672012
40.	P BakarakosI TheohariA NomikosImmunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomasHistopathology56876882201010.1111/j.1365-2559.2010.03570.x20636791
41.	ZY ChengXL GuoXY YangPTEN and rapamycin inhibiting the growth of K562 cells through regulating mTOR signaling pathwayJ Exp Clin Cancer Res2787200810.1186/1756-9966-27-8719115995
42.	BY ShorningD GriffithsAR ClarkeLkb1 and Pten synergise to suppress mTOR-mediated tumorigenesis and epithelial-mesenchymal transition in the mouse bladderPloS One6e16209201110.1371/journal.pone.001620921283818