Extracellular proteinase inhibitor-accelerated apoptosis is associated with B cell activating factor in mammary epithelial cells.
The expression of extracellular proteinase inhibitor (Expi) gene was induced during the involution of mammary gland, when apoptosis occurs in this tissue. Transient transfection of Expi gene partially induced apoptosis of mammary epithelial HC11 cells. We developed the stable cell lines overexpressing Expi gene and found that overexpression of Expi accelerated apoptosis of mammary epithelial cells under serum starvation. To understand apoptosis pathway involved in the Expi overexpression, we examined the gene expression profile by using apoptosis gene array containing 243 genes. The subsequent confirmation of the altered gene expression by northern analysis demonstrated that overexpression of the Expi gene induced expression of several genes, which included B cell activating factor (BAFF), Bax, cytochrome c, caspase-9, caspase-3, caspase-6, and CIDE-A. From this study, we first demonstrate that BAFF is involved in mammary apoptosis. Furthermore, we have found that the Expi-accelerated apoptosis is mediated via BAFF receptor among three known BAFF receptors: BAFF receptor, tumor necrosis factor (TNF) receptor homologue TACI (transmembrane activator and CAML-interactor), and BCMA (another TNFR homologue, B cell maturation antigen). Our studies also demonstrate that the use of apoptosis array provides an efficient tool to identify apoptosis pathway involved in gene transfection.
Jung
Dae Jun
DJ
Department of Applied Bioscience and Biotechnology, Biotechnology Research Institute, College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, South Korea.
Bong
Jin Jong
JJ
Baik
Myunggi
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011480:Protease Inhibitors / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D011480:Protease Inhibitors; D018124:Receptors, Tumor Necrosis Factor; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha