Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis

Autor: Rezan Fahrioglu Yamaci, Filippo Pani, Meral Koyutürk, Esra Battaloglu, William J. Brackenbury, Dimis Theodorou, Scott P. Fraser, Athina-Myrto Chioni, Zuzanna S. Siwy, Maria E. Mycielska, Handan Kaya, David S. Latchman, Jie Jiang, James K.J. Diss, Mustafa B. A. Djamgoz, Manuela Tamburo De Bella, R. Charles Coombes, Martin J. Slade, Zbigniew J. Grzywna, Monika Krasowska, Carlo Palmieri, Huiyan Pan, Robert S. Tolhurst
Přispěvatelé: Koyutürk, Meral
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Cancer Research
Pathology
medicine.medical_specialty
Patch-Clamp Techniques
Biopsy
Blotting
Western
Molecular Sequence Data
Voltage gated sodium channel
Motility
Breast Neoplasms
Tetrodotoxin
In Vitro Techniques
Biology
Sodium Channels
NAV1.5 Voltage-Gated Sodium Channel
Metastasis
Breast cancer
Cell Movement
In vivo
Cell Line
Tumor
medicine
Humans
Protein Isoforms
Neoplasm Invasiveness
Amino Acid Sequence
Breast
Neoplasm Metastasis
Cell Proliferation
Ions
Dose-Response Relationship
Drug
Reverse Transcriptase Polymerase Chain Reaction
Cancer
Epithelial Cells
medicine.disease
Immunohistochemistry
Endocytosis
Up-Regulation
Electrophysiology
Gene Expression Regulation
Neoplastic
Blot
Phenotype
Oncology
Tumor progression
Lymphatic Metastasis
Cancer cell
Disease Progression
Cancer research
Ion channel
Popis: Purpose: Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na+ channel (VGSC) expression and its possible role in human breast cancer. Experimental Design: Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC α-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCα expression and its association with metastasis in vivo. Results: VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Nav1.5, in its newly identified “neonatal” splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Nav1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Nav1.5 expression and clinically assessed lymph node metastasis. Conclusions: Up-regulation of neonatal Nav1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target.
Databáze: OpenAIRE
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