PEG10 Promoter-Driven Expression of Reporter Genes Enables Molecular Imaging of Lethal Prostate Cancer

被引:10
作者
Shapovalova, Mariya [1 ]
Lee, John K. [2 ]
Li, Yingming [3 ]
Vander Griend, Donald J. [3 ]
Coleman, Ilsa M. [2 ]
Nelson, Peter S. [2 ]
Dehm, Scott M. [4 ]
LeBeau, Aaron M. [1 ]
机构
[1] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA
[2] Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
[3] Univ Minnesota, Dept Lab Med & Pathol, Masonic Canc Ctr, Dept Urol, Minneapolis, MN 55455 USA
[4] Univ Illinois, Dept Pathol, Chicago, IL USA
关键词
2-STEP TRANSCRIPTIONAL AMPLIFICATION; RECEPTOR SPLICE VARIANTS; REAL-TIME PCR; ANDROGEN RECEPTOR; CASTRATION-RESISTANT; PRELIMINARY EFFICACY; DOSE-ESCALATION; PHASE; 1/2A; THERAPY; PROGRESSION;
D O I
10.1158/0008-5472.CAN-19-2181
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The retrotransposon-derived paternally expressed gene 10 (PEG10) protein is ordinarily expressed at high levels in the placenta. Recently, it was discovered that PEG10 isoforms promote the progression of prostate cancer to a highly lethal androgen receptor (AR)-negative phenotype. The presence of PEG10 in other subtypes of prostate cancer has not been explored and a utility for PEG10 overexpression has not been developed. Here, we found that in addition to AR-null disease, PEG10 was also expressed in prostate cancer with constitutively active AR-splice variants. A molecular genetic imaging strategy for noninvasive imaging of AR-splice variant prostate cancer was developed by utilizing the cancer specificity of the PEG10 promoter to drive the expression of reporter genes. Plasmid insertion of a PEG10 promoter sequence optimized for enhanced output upstream of a reporter gene allowed detection of prostate cancer by near-infrared and positron emission tomography imaging after systemic administration of the plasmid in vivo. PEG10 expressing subcutaneous xenograft and intratibial tumor models were imaged by both modalities using this molecular genetic imaging strategy. This study demonstrates a preclinical proof-of-concept that the PEG10 promoter is a powerful and specific tool that can be utilized for noninvasive detection of aggressive prostate cancer subtypes. Significance: PEG10 is expressed by prostate cancer with constitutively active AR-splice variants that can be exploited for noninvasive molecular imaging of this aggressive prostate cancer subytpe.
引用
收藏
页码:5668 / 5680
页数:13
相关论文
共 60 条
[1]   The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer [J].
Akamatsu, Shusuke ;
Wyatt, Alexander W. ;
Lin, Dong ;
Lysakowski, Summer ;
Zhang, Fan ;
Kim, Soojin ;
Tse, Charan ;
Wang, Kendric ;
Mo, Fan ;
Haegert, Anne ;
Brahmbhatt, Sonal ;
Bell, Robert ;
Adomat, Hans ;
Kawai, Yoshihisa ;
Xue, Hui ;
Dong, Xin ;
Fazli, Ladan ;
Tsai, Harrison ;
Lotan, Tamara L. ;
Kossai, Myriam ;
Mosquera, Juan Miguel ;
Rubin, Mark A. ;
Beltran, Himisha ;
Zoubeidi, Amina ;
Wang, Yuzhuo ;
Gleave, Martin E. ;
Collins, Colin C. .
CELL REPORTS, 2015, 12 (06) :922-936
[2]  
Ammannagari N, 2015, AM J HEMATOL-ONCOL, V11, P15
[3]   Neuroendocrine differentiation of prostate cancer leads to PSMA suppression [J].
Bakht, Martin K. ;
Derecichei, Iulian ;
Li, Yinan ;
Ferraiuolo, Rosa-Maria ;
Dunning, Mark ;
Oh, So Won ;
Hussein, Abdulkadir ;
Youn, Hyewon ;
Stringer, Keith F. ;
Jeong, Chang Wook ;
Cheon, Gi Jeong ;
Kwak, Cheol ;
Kang, Keon Wook ;
Lamb, Alastair D. ;
Wang, Yuzhuo ;
Dong, Xuesen ;
Porter, Lisa A. .
ENDOCRINE-RELATED CANCER, 2019, 26 (02) :131-146
[4]   Aggressive Variants of Castration-Resistant Prostate Cancer [J].
Beltran, Himisha ;
Tomlins, Scott ;
Aparicio, Ana ;
Arora, Vivek ;
Rickman, David ;
Ayala, Gustavo ;
Huang, Jiaoti ;
True, Lawrence ;
Gleave, Martin E. ;
Soule, Howard ;
Logothetis, Christopher ;
Rubin, Mark A. .
CLINICAL CANCER RESEARCH, 2014, 20 (11) :2846-2850
[5]   Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil [J].
Bettegowda, C ;
Foss, CA ;
Cheong, I ;
Wang, YC ;
Diaz, L ;
Agrawal, N ;
Fox, J ;
Dick, J ;
Dang, LH ;
Zhou, SB ;
Kinzler, KW ;
Vogelstein, B ;
Pomper, MG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (04) :1145-1150
[6]   Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression [J].
Bhang, Hyo-eun C. ;
Gabrielson, Kathleen L. ;
Laterra, John ;
Fisher, Paul B. ;
Pomper, Martin G. .
NATURE MEDICINE, 2011, 17 (01) :123-U302
[7]   MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease [J].
Bhanvadia, Raj R. ;
VanOpstall, Calvin ;
Brechka, Hannah ;
Barashi, Nimrod S. ;
Gillard, Marc ;
McAuley, Erin M. ;
Vasquez, Juan Manuel ;
Paner, Gladell ;
Chan, Wen-Ching ;
Andrade, Jorge ;
De Marzo, Angelo M. ;
Han, Misop ;
Szmulewitz, Russell Z. ;
Vander Griend, Donald J. .
CLINICAL CANCER RESEARCH, 2018, 24 (15) :3668-3680
[8]   AEG-1 Promoter-Mediated Imaging of Prostate Cancer [J].
Bhatnagar, Akrita ;
Wang, Yuchuan ;
Mease, Ronnie C. ;
Gabrielson, Matthew ;
Sysa, Polina ;
Minn, Il ;
Green, Gilbert ;
Simmons, Brian ;
Gabrielson, Kathleen ;
Sarkar, Siddik ;
Fisher, Paul B. ;
Pomper, Martin G. .
CANCER RESEARCH, 2014, 74 (20) :5772-5781
[9]   PD-L1 is highly expressed in Enzalutamide resistant prostate cancer [J].
Bishop, Jennifer L. ;
Sio, Alexander ;
Angeles, Arkhjamil ;
Roberts, Morgan E. ;
Azad, Arun A. ;
Chi, Kim N. ;
Zoubeidi, Amina .
ONCOTARGET, 2015, 6 (01) :234-242
[10]   The androgen/androgen receptor axis in prostate cancer [J].
Bluemn, Eric G. ;
Nelson, Peter S. .
CURRENT OPINION IN ONCOLOGY, 2012, 24 (03) :251-257