Activation of Stat3 in Primary Tumors from High-Risk Breast Cancer Patients Is Associated with Elevated Levels of Activated Src and Survivin Expression

Autor: Sandy Livingston, Craig A. Beam, Marek Wloch, Nills Diaz, Richard Jove, Tammy Bowman, Ibrahim Eweis, Susan Minton, Carlos A. Muro-Cacho, Ed Seijo, Roy Garcia, Charles E. Cox, Alan B. Cantor, Daniel M. Sullivan, Ji-Hyun Lee, Tanya Gritsko
Rok vydání: 2006
Předmět:
STAT3 Transcription Factor
Cancer Research
Receptor
ErbB-2
Survivin
medicine.medical_treatment
bcl-X Protein
Estrogen receptor
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Electrophoretic Mobility Shift Assay
Docetaxel
medicine.disease_cause
Inhibitor of Apoptosis Proteins
Clinical Trials
Phase II as Topic
Breast cancer
Risk Factors
Biomarkers
Tumor
Image Processing
Computer-Assisted
In Situ Nick-End Labeling
medicine
Humans
Epidermal growth factor receptor
Neoadjuvant therapy
biology
medicine.disease
Immunohistochemistry
Neoadjuvant Therapy
Neoplasm Proteins
Enzyme Activation
ErbB Receptors
Ki-67 Antigen
src-Family Kinases
Proto-Oncogene Proteins c-bcl-2
Receptors
Estrogen
Oncology
Doxorubicin
Cancer research
biology.protein
Female
Taxoids
Carcinogenesis
Microtubule-Associated Proteins
medicine.drug
Zdroj: Clinical Cancer Research. 12:20-28
ISSN: 1557-3265
1078-0432
Popis: Purpose: Constitutive activation of signal transducer and activator of transcription 3 (Stat3) protein has been observed in a wide variety of tumors, including breast cancer, and contributes to oncogenesis at least in part by prevention of apoptosis. In a study of 45 patients with high-risk breast cancer enrolled in a phase II neoadjuvant chemotherapy trial with docetaxel and doxorubicin, we evaluated the levels of Stat3 activation and potentially associated molecular biomarkers in invasive breast carcinoma compared with matched nonneoplastic tissues. Experimental Design: Using immunohistochemistry and image analysis, we quantified the levels of phospho-Stat3 (pY-Stat3), phospho-Src (pY-Src), epidermal growth factor receptor, HER2/neu, Ki-67, estrogen receptor, Bcl-2, Bcl-xL, Survivin, and apoptosis in formalin-fixed, paraffin-embedded sections from invasive carcinomas and their paired nonneoplastic parenchyma. The levels of molecular biomarkers in nonneoplastic and tumor tissues were analyzed as continuous variables for statistically significant correlations. Results: Levels of activated pY-Stat3 and pY-Src measured by immunohistochemistry were significantly higher in invasive carcinoma than in nonneoplastic tissue (P < 0.001). In tumors, elevated levels of pY-Stat3 correlated with those of pY-Src and Survivin. Levels of pY-Stat3 were higher in partial pathologic responders than in complete pathologic responders. In partial pathologic responders, pY-Stat3 levels correlated with Survivin expression. Conclusions: Our findings suggest important roles for elevated activities of Stat3 and Src, as well as Survivin expression, in malignant progression of breast cancer. Furthermore, elevated Stat3 activity correlates inversely with complete pathologic response. These findings suggest that specific Stat3 or Src inhibitors could offer clinical benefits to patients with breast cancer.
Databáze: OpenAIRE
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