Please use this identifier to cite or link to this item: https://doi.org/10.3892/ol.2018.8462
Title: Bacillus Calmette-Guerin induces rapid gene expression changes in human bladder cancer cell lines that may modulate its survival
Authors: Rahmat, Juwita N 
Esuvaranathan, Kesavan 
Mahendran, Ratha 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Bacillus Calmette-Guerin
gene expression
bladder cancer
cell lines
MYCOBACTERIUM-BOVIS
MURINE BLADDER
IMMUNOTHERAPY
MACROPHAGES
PATHWAY
TUMOR
INTERNALIZATION
INSTILLATION
ACTIVATION
AUGMENTS
Issue Date: 11-Apr-2018
Publisher: SPANDIDOS PUBL LTD
Citation: Rahmat, Juwita N, Esuvaranathan, Kesavan, Mahendran, Ratha (2018-04-11). Bacillus Calmette-Guerin induces rapid gene expression changes in human bladder cancer cell lines that may modulate its survival. ONCOLOGY LETTERS 15 (6) : 9231-9241. ScholarBank@NUS Repository. https://doi.org/10.3892/ol.2018.8462
Abstract: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard therapy for non-muscle invasive bladder cancer. The aim of the present study was to identify genes that are induced in response to BCG immunotherapy, as these may be potential biomarkers for the response to clinical therapy. To model clinical therapy, human bladder cancer cell lines were incubated with BCG (live or lyophilized BCG Connaught) for 2 h. RNA was extracted and evaluated by Representational Differential Analysis (RDA) and oligo arrays. Gene expression was confirmed by reverse transcription polymerase chain reaction on fresh cell lines with differential abilities to internalize BCG. The effect of 2 major BCG soluble proteins, antigen 85B (Ag85B) and Mycobacterium protein tyrosine phosphatase A (MptpA) and BCG Tice® on gene expression was also determined. GAPDH and β-actin, which are normally used as control genes, were upregulated by BCG. Therefore, the ribosomal RNA gene ribosomal protein S27a was used to normalize gene expression. The genes likely to be induced by BCG internalization and soluble factors were: GSTT2, MGST2, CCL20, TNFα, CCNE1 and IL10RB. Those induced by BCG membrane interactions and/or soluble factors were: MGST1, CXCL6, IL12A, CSF2, IL1β and TOLLIP. MptpA decreased GSTT2 expression, and Ag85B increased TNFα expression. The two BCG strains significantly increased GSTT2, TNFα and TOLLIP levels in MGH cells. However, in J82 cells there was a BCG strain-dependent difference in TNFα expression. An important outcome of the present study was the determination that neither GAPDH nor β-actin were suitable control genes for the analysis of BCG-induced gene expression. BCG Connaught and Tice® induced similar expression levels of genes in bladder cancer cell lines. BCG soluble proteins modulated gene expression and therefore may affect therapeutic outcomes. The genes identified may be novel biomarkers of the response to BCG therapy.
Source Title: ONCOLOGY LETTERS
URI: https://scholarbank.nus.edu.sg/handle/10635/208349
ISSN: 17921074
17921082
DOI: 10.3892/ol.2018.8462
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