scholarly journals Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Falko Lange ◽  
Benjamin Franz ◽  
Claudia Maletzki ◽  
Michael Linnebacher ◽  
Maja Hühns ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Small Molecule ◽  
Cell Biology ◽  
Kinase Inhibitors ◽  
Cancer Cell Lines ◽  
Multikinase Inhibitor ◽  
Primary Tumors ◽  
Low Passage

Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in anin vitrosetting. The mutantBRAF(V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 inBRAFmutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence ofKRAS, BRAF, PIK3CA, andTP53mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.

scholarly journals Characterization of novel low passage primary and metastatic colorectal cancer cell lines

Oncotarget ◽  
2016 ◽  
Vol 7 (12) ◽  
pp. 14499-14509 ◽  
Author(s):  
Arnoud Boot ◽  
Jaap van Eendenburg ◽  
Stijn Crobach ◽  
Dina Ruano ◽  
Frank Speetjens ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines ◽  
Low Passage

Characterization of FOXF1 as a novel regulator of nodal metastasis in bladder cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 480-480
Author(s):  
Anirban P Mitra ◽  
Andrea Kokorovic ◽  
Tanner Miest ◽  
Vikram M Narayan ◽  
Debasish Sundi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Differentially Expressed Gene ◽  
Cancer Cell Lines ◽  
Differentially Expressed ◽  
Bladder Cancer Cell ◽  
Primary Tumors ◽  
Orthotopic Xenografts

480 Background: Members of the forkhead transcription factor (FOX) family are important mediators of embryonic development and are known to be altered in a variety of cancers. The functional role of FOXF1 in bladder tumorigenesis and progression has not been clearly characterized thus far. This study investigated the clinical implications of differential FOXF1 expression in bladder cancer, and potential mechanisms by which its alteration can lead to tumor metastasis. Methods: Whole genome expression profiling was performed on paired primary tumors and nodal metastases from a radical cystectomy discovery cohort using Illumina HT12 v3-4 BeadChip arrays to identify FOXF1 as a top differentially expressed gene. Prognostic role of differential FOXF1 expression was validated on two independent cystectomy cohorts. Differential FOXF1 expression was also evaluated in murine orthotopic xenografts. Small interfering RNA was used to knock down FOXF1 in RT112 and UC6 bladder cancer cell lines to develop an in vitro model for assessment of metastatic potential. Next-generation sequencing and hierarchical clustering analysis were used to identify differentially altered genes secondary to FOXF1 knockdown. 186 biologically curated pathways were interrogated with internal validation to elucidate the downstream biologic mechanisms of metastasis. Results: In the discovery cohort, FOXF1 was a top differentially expressed gene with 3.6-fold lower expression in nodal metastases than paired primary tumors (n = 33, p < 0.001). Multivariable analyses in two validation cohorts (total n = 128) indicated that FOXF1 underexpression was associated with worse cancer-specific (p = 0.046) and overall survival (p = 0.006). Murine orthotopic xenografts (n = 13) established from human bladder cancer cell lines (UC3, UC6, UC14) showed FOXF1 underexpression in metastatic deposits compared with primary tumors (p = 0.004). Hierarchical clustering identified 40 differentially expressed genes between FOXF1-knockdown bladder cancer cell lines and their corresponding controls. Biological pathway interrogation showed differential enrichment for genes associated with mitogen-activated protein kinase signaling, focal adhesion and other carcinogenic pathways in FOXF1-knockdown cells compared with controls (normalized enrichment score ≥ 1.3). Conclusions: We identify and characterize FOXF1 as a novel regulatory molecule that potentially drives bladder cancer metastasis. This may be modulated through alterations in intracellular signaling and cellular adhesion. FOXF1 may serve as a prognostic biomarker that can identify patients at impending risk for metastasis who may benefit from more aggressive management.

IGF2 knockdown in two colorectal cancer cell lines decreases survival, adhesion and modulates survival-associated genes

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 12485-12495 ◽  
Author(s):  
Michael A. Rogers ◽  
Verena Kalter ◽  
Moritz Strowitzki ◽  
Martin Schneider ◽  
Peter Lichter
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines

EXTL3/EXTR1 alterations in colorectal cancer cell lines.

1999 ◽  
Author(s):  
T Arai ◽  
Y Akiyama ◽  
H Nagasaki ◽  
N Murase ◽  
S Okabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines

scholarly journals DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines

Oncogene ◽  
2000 ◽  
Vol 19 (7) ◽  
pp. 943-952 ◽  
Author(s):  
Martha M Pao ◽  
Gangning Liang ◽  
Yvonne C Tsai ◽  
Zhenggang Xiong ◽  
Peter W Laird ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines
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