In vivo longitudinal imaging of RNA interference-induced endocrine therapy resistance in breast cancer. J Biophotonics 2020 Jan;13(1):e201900180
Date
10/09/2019Pubmed ID
31595691Pubmed Central ID
PMC9229172DOI
10.1002/jbio.201900180Scopus ID
2-s2.0-85073971698 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Endocrine therapy resistance in breast cancer is a major obstacle in the treatment of patients with estrogen receptor-positive (ER+) tumors. Herein, we demonstrate the feasibility of longitudinal, noninvasive and semiquantitative in vivo molecular imaging of resistance to three endocrine therapies by using an inducible fluorescence-labeled short hairpin RNA (shRNA) system in orthotopic mice xenograft tumors. We employed a dual fluorescent doxycycline (Dox)-regulated lentiviral inducer system to transfect ER+ MCF7L breast cancer cells, with green fluorescent protein (GFP) expression as a marker of transfection and red fluorescent protein (RFP) expression as a surrogate marker of Dox-induced tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown. Xenografted MCF7L tumor-bearing nude mice were randomized to therapies comprising estrogen deprivation, tamoxifen or an ER degrader (fulvestrant) and an estrogen-treated control group. Longitudinal imaging was performed by a home-built multispectral imaging system based on a cooled image intensified charge coupled device camera. The GFP signal, which corresponds to number of viable tumor cells, exhibited excellent correlation to caliper-measured tumor size (P << .05). RFP expression was substantially higher in mice exhibiting therapy resistance and strongly and significantly (P < 1e-7) correlated with the tumor size progression for the mice with shRNA-induced PTEN knockdown. PTEN loss was strongly correlated with resistance to estrogen deprivation, tamoxifen and fulvestrant therapies.
Author List
Biswal NC, Fu X, Jagtap JM, Shea MJ, Kumar V, Lords T, Roy R, Schiff R, Joshi AAuthor
Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents, Hormonal
Breast Neoplasms
Cell Line, Tumor
Drug Resistance, Neoplasm
Female
Humans
Mice
Mice, Nude
RNA Interference
