|
| Status |
Public on Jun 01, 2006 |
| Title |
NF639 cells original population vs EGCG-resistant population |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor, and induction of multiple downstream signaling pathways including Akt kinase to NF-kappaB cascade that is associated with poor prognosis. Previously, we demonstrated green tea polyhenol epigallocatechin 3-gallate (EGCG) inhibits growth of NF639 Her-2/neu-driven breast cancer cells via reducing receptor autophosphorylation, and downstream Akt and NF-kappaB activities (Pianetti et al., 2002). Interestingly, we noted that upon prolonged culture in the presence of EGCG some cells developed resistance to the polyphenol. Here we report that resistant cells have lost tyrosine phosphorylation on the Her-2/neu receptor. Surprisingly, they displayed elevated NF-kappaB activity, and inhibition of this activity sensitized cells to EGCG. Data from microarray analysis of the original and resistant NF639 populations of cells were subjected to Gene Set Enrichment Analysis (GSEA) pathway analysis, which revealed that the mitogen activated protein kinase (MAPK) pathway was activated in the resistant cells. Treatment of the resistant cells with a combination of EGCG and the MAPK inhibitor U0216 dramatically reduced colony growth and mesenchymal phenotype. Thus, activation of the MAPK pathway mediates resistance to EGCG. Our studies suggest that gene expression profiling of drug resistant cells may provide a mechanism of determining effective systemic therapies for treatment of these advanced cancers.
Keywords: Drug resistance
|
| |
|
| Overall design |
Total RNA from original NF639 cells and EGCG resistant NF639 cells were harvested using the UltraspecII RNA isolation kit (Biotecx), following the manufacturer’s instruction. The RNA samples were submitted to Boston University Microarray Resource for microarray hybridization using Affymetrix Mouse 430A 2.0 chips. RNAs from two independent experiments were analyzed and data pooled for computational analysis.
|
| |
|
| Contributor(s) |
Guo S, Lu J, Subramanian A, Sonenshein GE |
| Citation(s) |
16707458 |
| Submission date |
Jan 31, 2006 |
| Last update date |
Jan 08, 2019 |
| Contact name |
Gail E Sonenshein |
| E-mail(s) |
gsonensh@bu.edu
|
| Phone |
617-638-4120
|
| Organization name |
Boston University Medical School
|
| Department |
Biochemistry
|
| Street address |
715 Albany Street
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA94987 |
Less...
More...