scholarly journals EMT markers gene expression in BPIFB2 overexpressed gastric cancer cell lines

2018 ◽  
Vol 29 ◽  
pp. ix55 ◽  
Author(s):  
Z. Karim ◽  
N.A. Zulkifli ◽  
S.H. Sheikh Abdul Kadir ◽  
K. Abd Khalil ◽  
M. Musa
BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Karolin Ebert ◽  
Gwen Zwingenberger ◽  
Elena Barbaria ◽  
Simone Keller ◽  
Corinna Heck ◽  
...  

Abstract Background Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. The molecular mechanisms of action for anti-HER-family drugs in gastric cancer cells are incompletely understood. We compared the molecular effects of trastuzumab and the other HER-family targeting drugs cetuximab and afatinib on phosphoprotein and gene expression level to gain insights into the regulated pathways. Moreover, we intended to identify genes involved in phenotypic effects of anti-HER therapies. Methods A time-resolved analysis of downstream intracellular kinases following EGF, cetuximab, trastuzumab and afatinib treatment was performed by Luminex analysis in the gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87. The changes in gene expression after treatment of the gastric cancer cell lines with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 h were analyzed by RNA sequencing. Significantly enriched pathways and gene ontology terms were identified by functional enrichment analysis. Furthermore, effects of trastuzumab and afatinib on cell motility and apoptosis were analyzed by time-lapse microscopy and western blot for cleaved caspase 3. Results The Luminex analysis of kinase activity revealed no effects of trastuzumab, while alterations of AKT1, MAPK3, MEK1 and p70S6K1 activations were observed under cetuximab and afatinib treatment. On gene expression level, cetuximab mainly affected the signaling pathways, whereas afatinib had an effect on both signaling and cell cycle pathways. In contrast, trastuzumab had little effects on gene expression. Afatinib reduced average speed in MKN1 and MKN7 cells and induced apoptosis in NCI-N87 cells. Following treatment with afatinib, a list of 14 genes that might be involved in the decrease of cell motility and a list of 44 genes that might have a potential role in induction of apoptosis was suggested. The importance of one of these genes (HBEGF) as regulator of motility was confirmed by knockdown experiments. Conclusions Taken together, we described the different molecular effects of trastuzumab, cetuximab and afatinib on kinase activity and gene expression. The phenotypic changes following afatinib treatment were reflected by altered biological functions indicated by overrepresentation of gene ontology terms. The importance of identified genes for cell motility was validated in case of HBEGF.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 50-50
Author(s):  
H. Chang ◽  
S. Y. Rha ◽  
H. Jeung ◽  
J. Ahn ◽  
J. Jung ◽  
...  

50 Background: We evaluated the cytotoxic effects of combining of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, with taxanes in human gastric cancer cell lines, and evaluated the pre-treatment difference of gene profile to identify genes that could potentially mediate the cytotoxic response. Methods: Twenty-five gastric cancer cell lines with 22K gene expression data were treated with SAHA and paclitaxel or docetaxel, and the synergistic interaction between the drugs was evaluated in vitro using the combination index (CI) method. We performed significance analysis of microarray (SAM) to identify chemosensitivity-related genes in gastric cancer cell lines that were concomitantly treated with SAHA and taxane. We generated a correlation-matrix between gene expression and CI values to identify genes whose expression correlated with a combined effect of taxanes and SAHA. Results: Taxane and SAHA combination had a synergistic cytotoxic effect against taxane-resistant gastric cancer cells. We selected 49 chemosensitivity-related genes, which were commonly identified in paclitaxel and docetaxel combined with SAHA, via SAM analysis. Among them, nine common genes (SLIT2, REEP2, EFEMP2, CDC42SE1, FSD1, POU1F1, ZNF79, ETNK1, and DOCK5) were extracted from the subsequent correlation-matrix analysis. Conclusions: Taxane and SAHA combination could be efficacious for the treatment of gastric cancer. The genes which were related with the synergistic response to taxane and SAHA could serve as surrogate biomarkers to predict the therapeutic response in gastric cancer patients. We are researching to determine the expression of the nine genes in malignant human gastric cancer tissue and to correlate them with clinical information. No significant financial relationships to disclose.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Karolin Ebert ◽  
Gwen Zwingenberger ◽  
Elena Barbaria ◽  
Simone Keller ◽  
Corinna Heck ◽  
...  

An amendment to this paper has been published and can be accessed via the original article.


2009 ◽  
Vol 155 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Hideyo Miyato ◽  
Joji Kitayama ◽  
Hiroharu Yamashita ◽  
Daisuke Souma ◽  
Masahiro Asakage ◽  
...  

Oncogene ◽  
2002 ◽  
Vol 21 (42) ◽  
pp. 6549-6556 ◽  
Author(s):  
Jiafu Ji ◽  
Xin Chen ◽  
Suet Yi Leung ◽  
Jen-Tsan A Chi ◽  
Kent Man Chu ◽  
...  

Digestion ◽  
2006 ◽  
Vol 74 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Jinyu Gu ◽  
Hirofumi Yamamoto ◽  
Xueying Lu ◽  
Chew Yee Ngan ◽  
Tadashi Tsujino ◽  
...  

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