Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor

被引：152

作者：

Memarzadeh, Sanaz ^{[1
]}

Xin, Li ^{[2
,3
,4
]}

Mulholland, David J. ^{[5
,6
]}

Mansukhani, Alka ^{[10
]}

Wu, Hong ^{[5
,6
]}

Teitell, Michael A. ^{[7
,8
]}

Witte, Owen N. ^{[2
,3
,4
,5
,6
,9
]}

机构：

[1] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Immunol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Mol Genet, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Mol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Dept Med & Pharmacol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Dept Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[10] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

来源：

CANCER CELL | 2007年 / 12卷 / 06期

关键词：

D O I：

10.1016/j.ccr.2007.11.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Enhanced mesenchymal expression of FGF10 led to the formation of multifocal PIN or prostate cancer. Inhibition of epithelial FGFR1 signaling using DN FGFR1 led to reversal of the cancer phenotype. A subset of the FGH10-induced carcinoma was serially transplantable. Paracrine FGH10 led to an increase in epithelial androgen receptor and synergized with cell-autonomous activated AKT. Our observations indicate that stromal FGF10 expression may facilitate the multifocal histology observed in prostate adenocarcinoma and suggest the FGH10/FGFR1 axis as a potential therapeutic target in treating hormone-sensitive or refractory prostate cancer. We also show that transient exposure to a paracrine growth factor may be sufficient for the initiation of oncogenic transformation.

引用

页码：572 / 585

页数：14

共 56 条

[1] Stromal fibroblasts in cancer initiation and progression [J].

Bhowmick, NA ;

Neilson, EG ;

Moses, HL .

NATURE, 2004, 432 (7015) :332-337

[2] TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia [J].

Bhowmick, NA ;

Chytil, A ;

Plieth, D ;

Gorska, AE ;

Dumont, N ;

Shappell, S ;

Washington, MK ;

Neilson, EG ;

Moses, HL .

SCIENCE, 2004, 303 (5659) :848-851

[3]

Bostwick D G, 1999, Semin Urol Oncol, V17, P222

[4] Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation [J].

Boxer, RB ;

Jang, JW ;

Sintasath, L ;

Chodosh, LA .

CANCER CELL, 2004, 6 (06) :577-586

[5] Molecular determinants of resistance to antiandrogen therapy [J].

Chen, CD ;

Welsbie, DS ;

Tran, C ;

Baek, SH ;

Chen, R ;

Vessella, R ;

Rosenfeld, MG ;

Sawyers, CL .

NATURE MEDICINE, 2004, 10 (01) :33-39

[6] Loss of TGF-β type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-α-, MSP- and HGF-mediated signaling networks [J].

Cheng, N ;

Bhowmick, NA ;

Chytil, A ;

Gorksa, AE ;

Brown, KA ;

Muraoka, R ;

Arteaga, CL ;

Neilson, EG ;

Hayward, SW ;

Moses, HL .

ONCOGENE, 2005, 24 (32) :5053-5068

[7] Essential role for oncogenic Ras in tumour maintenance [J].

Chin, L ;

Tam, A ;

Pomerantz, J ;

Wong, M ;

Holash, J ;

Bardeesy, N ;

Shen, Q ;

O'Hagan, R ;

Pantginis, J ;

Zhou, H ;

Horner, JW ;

Cordon-Cardo, C ;

Yancopoulos, GD ;

DePinho, RA .

NATURE, 1999, 400 (6743) :468-472

[8] Androgen receptors in prostate cancer [J].

Culig, Z ;

Klocker, H ;

Bartsch, G ;

Hobisch, A .

[9]

CULIG Z, 1994, CANCER RES, V54, P5474

[10] Androgen receptor - an update of mechanisms of action in prostate cancer [J].

Culig, Z ;

Hobisch, A ;

Bartsch, G ;

Klocker, H .

UROLOGICAL RESEARCH, 2000, 28 (04) :211-219

← 1 2 3 4 5 6 →