In vivo longitudinal imaging of RNA interference‐induced endocrine therapy resistance in breast cancer. Issue 1 (9th October 2019)

• Record Type: Journal Article
• Authors: Biswal, Nrusingh C.; Fu, Xiaoyong; Jagtap, Jaidip M.; Shea, Martin J.; Kumar, Vijetha; Lords, Tamika; Roy, Ronita; Schiff, Rachel; Joshi, Amit
• Is Part Of: Journal of biophotonics. Volume 13:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-10-09
• Subjects: breast cancer -- doxycycline -- endocrine therapy resistance -- fluorescence imaging -- GFP -- lentiviral -- PTEN knockdown -- RFP; Photonics -- Periodicals; Optical materials -- Periodicals; Optics -- Periodicals; Medical instruments and apparatus -- Periodicals; 621.3605
• DOI: 10.1002/jbio.201900180
• Languages: English
• ISSNs: 1864-063X

Abstract

Abstract: 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. Abstract : In vivo images of GFP and RFP channels for treatment with (A) −Dox and (B) +Dox in mice. C, The tumor exhibiting resistance to endocrine therapy has been demonstrated with typical images from ED + Dox and Ful + Dox. Dox, doxycycline; ED, estrogen deprivation; Ful, fulvestrant; GFP, green fluorescent protein; RFP, red fluorescent protein.