scholarly journals HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib

2016 ◽  
Vol 12 (6) ◽  
pp. 5363-5369 ◽  
Author(s):  
Jing Xu ◽  
Li Shen ◽  
Bi-Cheng Zhang ◽  
Wen-Hong Xu ◽  
Shu-Qin Ruan ◽  
...  
2013 ◽  
Author(s):  
Hideki Terai ◽  
Kenzo Soejima ◽  
Katsuhiko Naoki ◽  
Hiroyuki Yasuda ◽  
Ryosuke Satomi ◽  
...  

2012 ◽  
Vol 48 ◽  
pp. S84-S85
Author(s):  
S. La Monica ◽  
R. Alfieri ◽  
M. Bonelli ◽  
A. Cavazzoni ◽  
C. Fumarola ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2533-2533
Author(s):  
R. Dua ◽  
P. Nhonthachit ◽  
C. Rinehart ◽  
C. L. Arteaga ◽  
R. Nahta ◽  
...  

2533 Background: HER2 overexpression is associated with accelerated disease progression and poor prognosis in breast cancer. Trastuzumab, a monoclonal antibody targeting the extracellular domain of HER2, is effective in the treatment of metastatic breast cancer. However, most patients treated with trastuzumab eventually develop clinical resistance. To investigate the role of HER-family receptors in trastuzumab resistance, we measured HER-family receptor expression, dimerization, and phosphorylation in trastuzumab susceptible and resistant cell lines. Methods: Cell lysates from trastuzumab susceptible and resistant BT474 and SKBR3 cell lines were obtained from the Arteaga and Esteva laboratories. Proximity-based, multiplexed assays were used to detect and quantify HER1, HER2, and HER3 expression and phosphorylation levels, as well as HER1/HER1, HER1/HER2, HER1/HER3, HER2/HER2, and HER2/HER3 dimers. Samples were incubated with a mixture of HER specific antibodies conjugated either with fluorescent reporter tags (eTags), or biotin, which binds a reporter tag releasing agent (chemical scissor). Reporter molecules are released based on proximity to the scissor in a photochemical reaction and separated by capillary gel electrophoresis. Results: In comparison to trastuzumab susceptible parental cell lines, both SKBR3 and BT474 trastuzumab-resistant cell lines displayed upregulated HER1 expression. Resistant BT474 cell lines exhibited markedly increased levels of HER1/HER2 heterodimers. Increases in HER2 phosphorylation in the trastuzumab resistant SKBR3 cell line were observed, consistent with previous studies implicating trastuzumab in the induction of HER2 phosphorylation. Total HER2 and HER3 levels were similar in trastuzumab susceptible and resistant BT474 cell lines. Conclusions: The development of trastuzumab resistance in these cell line models correlated with HER1 expression and the appearance of HER1:HER2 dimers. Since signaling initiated by such heterodimers is ineffectively antagonized by trastuzumab, these data suggest that selection for proliferative signaling mediated by HER1:HER2 dimers may represent a mechanism of trastuzumab resistance in breast cancer. No significant financial relationships to disclose.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qian Jin ◽  
Jisheng Zheng ◽  
Ming Chen ◽  
Na Jiang ◽  
Xianrong Xu ◽  
...  

Background. Acquired resistance occurred in the majority of nonsmall cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation of the HIF-1 pathway. Therefore, we examined the influence of the hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib. Methods. We established HCC827 GR cell line with MET amplification and set four groups with different treatment. An MTT assay, a colony formation analysis, and a wound healing assay were performed to determine the sensitivity change of HCC827 GR cells after different treatments. HIF-1α, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1α, p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson’s correlation analysis. Results. HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1α level, while there was no correlation between p-Met level and p-EGFR level. Conclusion. HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.


2014 ◽  
Vol 46 (1) ◽  
pp. 430-436 ◽  
Author(s):  
HIDEKI TERAI ◽  
KENZO SOEJIMA ◽  
HIROYUKI YASUDA ◽  
TAKASHI SATO ◽  
KATSUHIKO NAOKI ◽  
...  

Author(s):  
E.C. Chew ◽  
C.L. Li ◽  
D.P. Huang ◽  
H.C. Ho ◽  
L.S. Mak ◽  
...  

An epithelial cell line, NPC/HK1, has recently been established from a biopsy specimen of a recurrent tumour of the nasopharynx which was histologically diagnosed as a moderately to well differentiated squamous cell carcinoma. A definite decrease in the amount of tonofilaments and desmosomes in the NPC/HK1 cells during the cell line establishment was observed. The present communication reports on the fine structures of the NPC/HK1 cells heterotraneplanted in athymic nude mice.


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