The TGF-β, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer

被引：81
作者：
Assinder, Stephen J. [2 ,3 ]
Dong, Qihan [3 ,4 ]
Kovacevic, Zaklina [1 ,3 ]
Richardson, Des R. [1 ,3 ]
机构：
[1] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia
[2] Univ Sydney, Sch Med Sci, Discipline Physiol, Sydney, NSW 2006, Australia
[3] Univ Sydney, Bosch Inst, Prostate Canc Focus Grp, Sydney, NSW 2006, Australia
[4] Univ Sydney, Cent Clin Sch, Discipline Med, Sydney, NSW 2006, Australia
来源：
BIOCHEMICAL JOURNAL | 2009年 / 417卷
基金：
英国医学研究理事会; 澳大利亚研究理事会;
关键词：
N-myc downstream regulated gene-1 (NDRG-1); oncogenesis; phosphatase and tensin homologue deleted on chromosome 10 (PTEN); phosphoinositide 3-kinase/protein kinase B (PI3K/Akt); transforming growth factor-beta (TGF-beta); tumour suppression; GROWTH-FACTOR-BETA; METASTASIS SUPPRESSOR GENE; HYPOXIA-INDUCIBLE TRANSCRIPTION; SELECTIVE ANTITUMOR-ACTIVITY; FACTOR-BINDING PROTEIN-2; INDUCED AKT ACTIVATION; KINASE-B-GAMMA; ARACHIDONIC-ACID; CELL-CYCLE; IRON CHELATORS;
D O I：
10.1042/BJ20081610
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A key to the development of improved pharmacological treatment strategies for cancer is tin understanding of the integration of biochemical pathways involved in both tumorigenesis and cancer suppression. Furthermore, genetic markers that may predict the outcome of targeted pharmacological intervention in an individual are central to patient-focused treatment regimens rather (than file traditional 'one size fits all' approach. Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is a holy grail. This review will describe the evidence that demonstrates the integration of three established pathways: the tumour-suppressive TGF-beta (transforming growth facti pathway, the tumorigenic PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathway and the tumour-suppressive PTEN (phosphatase and tensin homologue deleted oil chromosome 10) pathway. It will discuss gene polymorphisms and somatic mutations in relevant genes and highlight novel pharmaceutical agents that target key points in these integrated pathways.
引用
收藏
页码：411 / 421
页数：11
相关论文
共 128 条
[1]  
ASSINDER SJ, 2007, MALE REPROD DYSFUNCT, P499
[2]   Transgelin: An actin-binding protein and tumour suppressor [J].
Assinder, Stephen J. ;
Stanton, Jo-Ann L. ;
Prasad, Priya D. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2009, 41 (03) :482-486
[3]   A critical role of tropomyosins in TGF-β regulation of the actin cytoskeleton and cell motility in epithelial cells [J].
Bakin, AV ;
Safina, A ;
Rinehart, C ;
Daroqui, C ;
Darbary, H ;
Helfman, DM .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (10) :4682-4694
[4]   PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer [J].
Bandyopadhyay, S ;
Pai, SK ;
Hirota, S ;
Hosobe, S ;
Tsukada, T ;
Miura, K ;
Takano, Y ;
Saito, K ;
Commes, T ;
Piquemal, D ;
Watabe, M ;
Gross, S ;
Wang, Y ;
Huggenvik, J ;
Watabe, K .
CANCER RESEARCH, 2004, 64 (21) :7655-7660
[5]   Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression [J].
Bandyopadhyay, S ;
Pai, SK ;
Hirota, S ;
Hosobe, S ;
Takano, Y ;
Saito, K ;
Piquemal, D ;
Commes, T ;
Watabe, M ;
Gross, SC ;
Wang, Y ;
Ran, S ;
Watabe, K .
ONCOGENE, 2004, 23 (33) :5675-5681
[6]  
Bandyopadhyay S, 2003, CANCER RES, V63, P1731
[7]   The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin [J].
Baron, V ;
Adamson, ED ;
Calogero, A ;
Ragona, G ;
Mercola, D .
CANCER GENE THERAPY, 2006, 13 (02) :115-124
[8]   Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia [J].
Berger, AP ;
Kofler, K ;
Bektic, J ;
Rogatsch, H ;
Steiner, H ;
Bartsch, G ;
Klocker, H .
PROSTATE, 2003, 57 (01) :57-65
[9]   AKT1E17K in human solid tumours [J].
Bleeker, F. E. ;
Felicioni, L. ;
Buttitta, F. ;
Lamba, S. ;
Cardone, L. ;
Rodolfo, M. ;
Scarpa, A. ;
Leenstra, S. ;
Frattini, M. ;
Barbareschi, M. ;
Del Grammastro, M. ;
Sciarrotta, M. G. ;
Zanon, C. ;
Marchetti, A. ;
Bardelli, A. .
ONCOGENE, 2008, 27 (42) :5648-5650
[10]   NHERFs, NEP, MAGUKs, and more: Interactions that regulate PTEN [J].
Bonifant, Challice L. ;
Kim, Jung-Sik ;
Waldman, Todd .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2007, 102 (04) :878-885
12345678910