Secreted frizzled related protein 2 (sFRP2) decreases susceptibility to UV-induced apoptosis in primary culture of canine mammary gland tumors by NF-κB activation or JNK suppression.
Resource
Breast Cancer Research and Treatment (SCI),100,49-58.
Journal
Breast Cancer Research and Treatment (SCI)
Journal Issue
100
Pages
49-58
Date Issued
2006-11
Date
2006-11
Author(s)
Abstract
Tumor formation can result from a decrease in cell death, as well as an increase in cell proliferation. In spite of the high incidence of mammary gland tumors (MGTs) in female dogs, the understanding of its etiology is still poor. Consistent with several proto-oncogenes (such as Wnt) for the mammary gland, sFRP2 is expressed in canine MGTs which is normally silent in the mammary gland. To elucidate the roles of SFRP2 in the tumorigenesis of MGTs, apoptosis regulation mediated by sFRP2 was investigated by overexpression of sFRP2 in MGT cells. DNA fragmentation and TUNEL assays showed a decreased susceptibility of the cells to UV-induced apoptosis in the context of sFRP2 overexpression. To analyze the pathways through which sFRP2 transduces anti-apoptosis signals, multiple-color immunofluorescence staining, immunoprecipitation, and immunoblotting were carried out. sFRP2 was found co-localized in the extracellular matrix of MGTs and the tyrosine phosphorylation of FAK was enhanced. Moreover, JNK was suppressed and NF-kB was activated in the cells expressing sFRP2 after UV-induced apoptosis analyzed by immunoblotting and electrophoretic mobility shift assay (EMSA). Taken together, these results suggest that sFRP2 exerts its anti-apoptotic function in mammary cancer cells through NF-κB activation or JNK suppression. ? Springer Science+Business Media B.V. 2006.
SDGs
Other Subjects
DNA fragment; immunoglobulin enhancer binding protein; membrane protein; SFRP2 protein, human; stress activated protein kinase; animal; apoptosis; article; cell culture; dog; experimental neoplasm; female; gene expression regulation; genetic transfection; genetics; metabolism; nick end labeling; pathology; physiology; signal transduction; ultraviolet radiation; Animals; Apoptosis; DNA Fragmentation; Dogs; Female; Gene Expression Regulation, Neoplastic; In Situ Nick-End Labeling; JNK Mitogen-Activated Protein Kinases; Mammary Neoplasms, Animal; Membrane Proteins; NF-kappa B; Signal Transduction; Transfection; Tumor Cells, Cultured; Ultraviolet Rays