Abstract 64P
Background
The prevalence of bladder cancer (BC) has been increasing worldwide. Particularly, patients carrying the Basal/Squamous BC (BSBC) have poor prognosis. Mammalian models such as cultured human BSBC cells and their xenografts have provided critical insights into its mechanisms, but effective therapeutics for BSBC is still lacking. Recently, the fruit fly Drosophila has made significant contributions to cancer research. Here, we employed Drosophila to generate the first fly model reproducing the BSBC genotypes and to discover novel therapeutic candidates for BSBC treatment.
Methods
BSBC often harbors mutations in genes ‘A’, ‘B’ and/or ‘C’. To model various alteration patterns in Drosophila, we employed the binary GAL4/UAS system, which targets expression of exogenous transgenes to a desired fly tissue. We prepared GAL4 driver strains expressing a transcription factor GAL4 specifically in the eye cells and wing cells (GMR-GAL4 and nub-GAL4, respectively, for validating transgene functions), or the Malpighian tubule which corresponds to human bladder (for modeling BSBC genotypes). We also generated UAS transgenic strains which carry mutated cDNA and/or shRNA sequences as transgenes downstream of the GAL4 target UAS sequence.
Results
Previous studies have reported that induction of wild-type A in fly eyes causes ‘rough eye’ phenotype by promoting apoptosis, which we confirmed using the eye-specific GMR-GAL4 driver. We found that additional expression of missense-mutated A or knockdown of A by shRNA rescued the phenotype as expected. Furthermore, we confirmed that overexpression of B using the same driver increased the fly eye size as previously reported. Using the wing-specific nub-GAL4 driver, we validated that knockdown of C by shRNA reduced the fly wing area, verifying its reported function to control tissue growth.
Conclusions
The eye and wing phenotypes induced by transgenes were consistent with their reported functions and our expectation, proving our strategy effective in validating functions of the transgenes and in modeling the BSBC genotypes in flies. We will next perform whole-body assays such as comprehensive genetic and drug screenings using these flies to demonstrate the mechanisms of BSBC pathogenesis and to develop novel BSBC treatments.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
45P - Therapeutic potential of ISM8207: A novel QPCTL inhibitor, in triple-negative breast cancer and B-cell non-Hodgkin lymphoma
Presenter: Sujata Rao
Session: Poster session 09
46P - Effect of coadministration of antioxidant chlorophyllin with docetaxel on invasion and metastasis in triple-negative breast cancer in vivo/in vitro
Presenter: Ayse Burus
Session: Poster session 09
47P - An ozone delivery system by cisplatin prodrug self-assembling micelles combining microwave to sensitizing immune checkpoint inhibitor in triple-negative breast cancer
Presenter: Dan Zheng
Session: Poster session 09
48P - Non-steroid anti-inflammatory treatment enhances the efficacy of modulated electro hyperthermia on triple-negative breast cancer and melanoma cancer models in vivo
Presenter: Nino Giunashvili
Session: Poster session 09
49P - Circulating miRNA signatures to predict recurrence in patients with pathological complete response of triple-negative breast cancer
Presenter: Ana Julia de Freitas
Session: Poster session 09
50P - Application and mechanism of tarloxotinib in HER2-positive breast cancer
Presenter: Xinyi Shao
Session: Poster session 09
51P - Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic breast tumour therapy by glutamine deprivation and cascading thrombosis
Presenter: Liqiang Zhou
Session: Poster session 09
53P - Treatment of cancer cells based on circulating tumor cell’s expression profile using off-label drugs
Presenter: Panagiotis Apostolou
Session: Poster session 09
54P - Enhanced oxidative phosphorylation of metastasis-initiating cells facilitates esophageal tumor cell seeding in lymph nodes
Presenter: Shanshan Li
Session: Poster session 09
55P - Transcriptional profiles of engineered T cells stimulated with different receptor structures and co-stimulatory domains
Presenter: Ungue Shin
Session: Poster session 09