scholarly journals Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines

2012 ◽  
Vol 23 (7) ◽  
pp. 1788-1795 ◽  
Author(s):  
D.M. Collins ◽  
N. O'Donovan ◽  
P.M. McGowan ◽  
F. O'Sullivan ◽  
M.J. Duffy ◽  
...  
Author(s):  
Danielle D. Jandial ◽  
Lauren S. Krill ◽  
Lixia Chen ◽  
Chunli Wu ◽  
Yu Ke ◽  
...  

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl2, Bclx/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.


Life Sciences ◽  
2010 ◽  
Vol 86 (17-18) ◽  
pp. 668-675 ◽  
Author(s):  
Elisa Pierpaoli ◽  
Valentina Viola ◽  
Francesca Pilolli ◽  
Marta Piroddi ◽  
Francesco Galli ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21174-21174
Author(s):  
D. Kostyal ◽  
T. Shay ◽  
C. Lanning ◽  
K. Horton ◽  
S. Welt ◽  
...  

21174 Background: Gene array technology was used to investigate Trastuzumab (T) induced molecular expression patterns in HER/2 amplified breast cancer cell lines. A variety of over-expressed and aberrantly expressed proteins were identified. Further analysis of these data demonstrated potential candidate target proteins for T-cell immunotherapy. The advantages of utilizing gene array analysis to identify target proteins for immunotherapy include rapid data generation and analysis, statistical confidence and reproducibility. Methods: BT 474 and SK-BR3 breast cancer cell lines contain the HER/2 amplicon. Under growth conditions demonstrating inhibitory effects of T (0.25–50 micrograms/ml), RNA extracts from treated and untreated cells were analyzed and compared by whole human genome, gene array analysis. Results: Three sperm associated proteins were found to be expressed in these breast cancer cell lines. In comparison to the HER/2 expression, sperm associated antigen-1 (saa-1) was found to be expressed at very high levels, approximately 30–40% the level of HER/2. Furthermore, treatment of breast cancer cell lines with T did not reduce the level of saa-1 expression. Two other aberrantly expressed genes were also identified, sperm associated antigen 8 (saa-8) and sperm associated antigen-14 (saa-14). Unlike saa-1, both saa-8 and saa-14 expression were down regulated by T treatments. Conclusions: Breast cancer patients with HER/2 over expressing tumors have a poorer prognosis. T treatment is an important part of the clinical management of these patients especially early in their course. The immunotherapy targets described here may further improve outcomes of T treatments and for T resistant disease when utilized as vaccines. These proteins are components of sperm acrosomes and whether they play a role in invasion and metastases is under investigation. No significant financial relationships to disclose.


2013 ◽  
Vol 89 (5) ◽  
pp. 319-325 ◽  
Author(s):  
Ioannis F. Voutsas ◽  
Louisa G. Mahaira ◽  
Katerina Fotopoulou ◽  
Nikiforos Kapranos ◽  
John G. Reclos ◽  
...  

1993 ◽  
Vol 168 (1) ◽  
pp. 228-232 ◽  
Author(s):  
Gustavo C. Rodriguez ◽  
Matthew P. Boente ◽  
Andrew Berchuck ◽  
Regina S. Whitaker ◽  
Kathy C. O’Briant ◽  
...  

2005 ◽  
Vol 115 (4) ◽  
pp. 519-527 ◽  
Author(s):  
Edward Htun van der Horst ◽  
Marta Murgia ◽  
Martin Treder ◽  
Axel Ullrich

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