Genomic characterization of three urinary bladder cancer cell lines: understanding genomic types of urinary bladder cancer

Abstract

Several genomic regions are frequently altered and associated with the type, stage and progression of urinary bladder cancer (UBC). We present the characterization of 5637, T24 and HT1376 UBC cell lines by karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. Some cytogenetic anomalies present in UBC were found in the three cell lines, such as chromosome 20 aneuploidy and the loss of 9p21. Some gene loci losses (e.g. CDKN2A) and gains (e.g. HRAS, BCL2L1 and PTPN1) were coincident across all cell lines. Although some significant heterogeneity and complexity were detected between them, their genomic profiles exhibited a similar pattern to UBC. We suggest that 5637 and HT1376 represent the E2F3/RB1 pathway due to amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of the remaining copy. The HT1376 presented a 10q deletion involving PTEN region and no alteration of PIK3CA region which, in combination with the inactivation of TP53, bears more invasive and metastatic properties than 5637. The T24 belongs to the alternative pathway of FGFR3/CCND1 by presenting mutated HRAS and over-represented CCND1. These cell lines cover the more frequent subtypes of UBC and are reliable models that can be used, as a group, in preclinical studies.

Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells

“…5637 cells well represent the E2F3/RB1 pathway due to amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of the other copy. The T24 cell line belongs to the alternative pathway of FGFR3/CCND1 by mutated HRAS and over-represented CCND1 (34). Viability and clonogenic data indicated that T24 cells were more prone to the toxic effect of EVOOE compared to 5367 cells, and these data were further supported by cell cycle analyses which highlighted that both cell lines were arrested in the G2/M phase but with a different mechanism which resulted in apoptotic death only for T24 cells, with a consistent increase in the sub-G1 peak that was not evidenced in 5637 cells.…”

“…Data confirmed the activation of apoptosis only in the T24 cells and only at high EVOOE doses, confirming the cytofluorimetric evidence. This different behavior of the two cell lines in response to EVOOE treatment, can be explained by the different mutational status in various key genes involved in cell proliferation regulation (34). The induction of programmed cell death only in T24 can also explain the different susceptibility to the cytotoxic action of EVOOE, as demonstrated by the difference in the decrease in viability observed in our experiments (Fig.…”

Identification of a multi-cancer gene expression biomarker for cancer clinical outcomes using a network-based algorithm

“…For instance, high expression of CALR has been associated with high risk in bladder cancer67. HRAS gains have been found in bladder cancer cell lines and have been related to urothelial tumorigenesis68. ITGA4 is part of a methylation gene set used for the detection of bladder cancer69.…”

Diagnostic and prognostic value of circulating miR-18a in the plasma of patients with gastric cancer

“…Another research in breast cancer found that miR-18a impairs DNA damage response through downregulation of ataxia-telangiectasia mutated kinase [30]. On the other hand, data from a research in bladder cancer indicated that miR-18a functioned as a tumor suppressor by targeting Dicer in T24 cells and revealed a noteworthy feedback loop, which may be utilized by the miR-17-92 cluster to control miRNA output and prevent its overexpression [31,32].…”