Secreted frizzled related protein 2 (sFRP2) decreases susceptibility to UV-induced apoptosis in primary culture of canine mammary gland tumors by NF-kappaB activation or JNK suppression.
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-kappaB activation or JNK suppression.
Lee
Jia-Lin
JL
Department and Graduate Institute of Veterinary Medicine, College of Bio-resources and Agriculture, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 106, Taiwan.
Chang
Ching-Jin
CJ
Chueh
Ling-Ling
LL
Lin
Chung-Tien
CT
D000818:Animals; D017209:Apoptosis; D053938:DNA Fragmentation; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D000094742:Secreted Frizzled-Related Proteins
D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D016328:NF-kappa B; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins