Abstract
Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses.
Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms.
Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice.
Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect.
Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.
Keywords: Apoptosis, breast adenocarcinoma, migration, proliferation, SOX4, tumorigenesis.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[http://dx.doi.org/10.1016/j.annepidem.2019.10.006] [PMID: 31753691]
[http://dx.doi.org/10.2174/1381612825666190705205155] [PMID: 31298161]
[http://dx.doi.org/10.1634/theoncologist.9-4-361] [PMID: 15266090]
[PMID: 22247839]
[http://dx.doi.org/10.3322/caac.21320] [PMID: 26513636]
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[http://dx.doi.org/10.1158/1055-9965.EPI-15-0578] [PMID: 26667886]
[http://dx.doi.org/10.1016/S1470-2045(13)70567-9] [PMID: 24872111]
[http://dx.doi.org/10.1371/journal.pgen.1008531] [PMID: 31895944]
[http://dx.doi.org/10.1007/s11596-019-2131-2] [PMID: 31845230]
[http://dx.doi.org/10.1186/s12920-019-0609-1] [PMID: 31703592]
[http://dx.doi.org/10.1016/S1534-5807(02)00223-X] [PMID: 12194848]
[http://dx.doi.org/10.1242/jcs.003855] [PMID: 17652162]
[http://dx.doi.org/10.4049/jimmunol.1202736] [PMID: 23345330]
[http://dx.doi.org/10.1038/ni.2362] [PMID: 22751141]
[http://dx.doi.org/10.1007/s13277-015-4756-5] [PMID: 26768610]
[http://dx.doi.org/10.1007/s11596-016-1565-z] [PMID: 27072961]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1868] [PMID: 26701805]
[http://dx.doi.org/10.1007/s10549-017-4139-2] [PMID: 28176176]
[http://dx.doi.org/10.1007/s13277-015-3051-9] [PMID: 25592378]
[http://dx.doi.org/10.2174/1574892811666160822161157] [PMID: 27549139]
[http://dx.doi.org/10.2174/1574892814666181231142136] [PMID: 30599110]
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[http://dx.doi.org/10.3892/ijo.2019.4832] [PMID: 31268162]
[http://dx.doi.org/10.1016/j.trecan.2017.06.002] [PMID: 28780934]
[http://dx.doi.org/10.1242/dev.042101] [PMID: 20147379]
[http://dx.doi.org/10.1038/380711a0] [PMID: 8614465]
[http://dx.doi.org/10.1155/2015/658141] [PMID: 26578818]
[http://dx.doi.org/10.1186/s12883-014-0207-y] [PMID: 25366337]
[http://dx.doi.org/10.1007/s11010-014-2315-9] [PMID: 25567207]
[http://dx.doi.org/10.1007/s11596-011-0491-3] [PMID: 21823023]
[http://dx.doi.org/10.1038/cddis.2015.290] [PMID: 26583330]
[http://dx.doi.org/10.1007/s12032-019-1317-6] [PMID: 31560094]
[http://dx.doi.org/10.1007/s12094-015-1337-4] [PMID: 26250764]
[http://dx.doi.org/10.1038/onc.2012.506] [PMID: 23246969]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3456] [PMID: 16585165]
[http://dx.doi.org/10.1186/1471-2121-12-50] [PMID: 22098624]
[http://dx.doi.org/10.1016/j.biopha.2017.01.084] [PMID: 28282784]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2730] [PMID: 17606719]
[http://dx.doi.org/10.1038/s41420-019-0142-1] [PMID: 30701088]
[http://dx.doi.org/10.1038/cddis.2014.226] [PMID: 24874738]