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Updated: Jun 13, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors
Maria Antonietta Lucci1, Rosaria Orlandi, Tiziana Triulzi
1Department of Experimental Pathology, University of Pisa, Pisa, Italy.
Background:
HER2-overexpression promotes malignancy by modulating signalling molecules, which include PTPs/DSPs (protein tyrosine and dual-specificity phosphatases). Our aim was to identify PTPs/DSPs displaying HER2-associated expression alterations.
Methods:
HER2 activity was modulated in MDA-MB-453 cells and PTPs/DSPs expression was analysed with a DNA oligoarray, by RT-PCR and immunoblotting. Two public breast tumor datasets were analysed to identify PTPs/DSPs differentially expressed in HER2-positive tumors.
Results:
In cells (1) HER2-inhibition up-regulated 4 PTPs (PTPRA, PTPRK, PTPN11, PTPN18) and 11 DSPs (7 MKPs [MAP Kinase Phosphatases], 2 PTP4, 2 MTMRs [Myotubularin related phosphatases]) and down-regulated 7 DSPs (2 MKPs, 2 MTMRs, CDKN3, PTEN, CDC25C); (2) HER2-activation with EGF affected 10 DSPs (5 MKPs, 2 MTMRs, PTP4A1, CDKN3, CDC25B) and PTPN13; 8 DSPs were found in both groups. Furthermore, 7 PTPs/DSPs displayed also altered protein level. Analysis of 2 breast cancer datasets identified 6 differentially expressed DSPs: DUSP6, strongly up-regulated in both datasets; DUSP10 and CDC25B, up-regulated; PTP4A2, CDC14A and MTMR11 down-regulated in one dataset.
Conclusions:
Several DSPs, mainly MKPs and, unexpectedly, MTMRs, were altered following HER2-modulation in cells and 3 DSPs (DUSP6, CDC25B and MTMR11) were altered in both cells and tumors. Among these, DUSP6, strongly up-regulated in HER2-positive tumors, would deserve further investigation as tumor marker or potential therapy target.
Insights
This study identified protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) altered by HER2 signaling in breast cancer cells and tumors. DUSP6, CDC25B, and MTMR11 were significantly altered, with DUSP6 showing promise as a therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- HER2-overexpression drives cancer malignancy by altering signaling molecules, including protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs).
- Understanding these alterations is crucial for identifying new therapeutic targets in HER2-positive cancers.
Purpose of the Study:
- To identify PTPs/DSPs with expression changes associated with HER2 activity.
- To investigate the role of these phosphatases in HER2-driven breast cancer.
Main Methods:
- HER2 activity was modulated in MDA-MB-453 cells.
- Gene and protein expression of PTPs/DSPs were analyzed using DNA oligoarrays, RT-PCR, and immunoblotting.
- Public breast tumor datasets were analyzed to correlate PTP/DSP expression with HER2 status.
Main Results:
- HER2 inhibition or activation altered the expression of numerous PTPs/DSPs, including MAP Kinase Phosphatases (MKPs) and Myotubularin related phosphatases (MTMRs).
- Seven PTPs/DSPs showed altered protein levels.
- Analysis of tumor datasets revealed differential expression of six DSPs, with DUSP6 strongly upregulated in HER2-positive tumors.
Conclusions:
- Several DSPs, particularly MKPs and MTMRs, are modulated by HER2 signaling.
- DUSP6, CDC25B, and MTMR11 were altered in both cellular models and tumors.
- DUSP6 warrants further investigation as a potential biomarker or therapeutic target in HER2-positive breast cancer.
