Role of PTP1B in HER2 Signaling in Breast Cancer

The receptor tyrosine kinase HER2/ ErbB2 is overexpressed in about 25% of all breast cancers, and presents an attractive therapeutic target. However, drug resistance is a significant clinical problem with current ErbB2-targeted therapies. The development of novel therapeutic strategies demands knowl...

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Bibliographic Details
Main Author: Saha, Sayanti
Format: Report
Language:English
Subjects:
ACIDS
BREAST CANCER
CELLS(BIOLOGY)
CLINICAL MEDICINE
COUPLING(INTERACTION)
CULTURES(BIOLOGY)
DRUGS
EPITHELIUM
HUMANS
IN VIVO ANALYSIS
MAMMARY GLANDS
MARKERS
Medicine and Medical Research
MOLECULAR PROPERTIES
ONCOGENES
PHOSPHATASES
PHOSPHORUS TRANSFERASES
PROTEINS
RECEPTOR SITES(PHYSIOLOGY)
REDUCTION
SENSE ORGANS
SIGNAL TRANSDUCTION
SIGNALS
STRATEGY
TARGETS
THERAPY
TRACER STUDIES
TYROSINE
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Summary:The receptor tyrosine kinase HER2/ ErbB2 is overexpressed in about 25% of all breast cancers, and presents an attractive therapeutic target. However, drug resistance is a significant clinical problem with current ErbB2-targeted therapies. The development of novel therapeutic strategies demands knowledge of ErbB2 receptor cross-talk with other signaling pathways. Recent reports have shown that Protein Tyrosine Phosphatase 1B (PTP1B) plays a positive role in ErbB2-induced breast cancer in vitroand in vivo. This research aims to understand the role of PTP1B-regulated pathways in ErbB2-mediated progression of breast cancer. The study uses quantitative proteomics to identify pro-oncogenic PTP1B substrates in ErbB2- transformed human mammary epithelial cells. Two cell populations-one with normal PTP1B expression (ErbB2/PTP1B+) and the other with reduced PTP1B expression (ErbB2/PTP1B-) were subjected to SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) coupled with quantitative phospho-proteomic analysis, which generated a raw list of about 1000 proteins. Future work will involve the use of an in vivosubstrate trapping method to identify direct PTP1B substrates. From the present study, we hope to determine the molecular mechanisms by which PTP1B regulates ErbB2-induced breast carcinogenesis, with the ultimate aim of identifying new therapeutic targets and new biomarkers for breast cancer.