侵袭性乳腺癌 (BC) 细胞高表达 Rho GTP 酶激活蛋白 29 (ARHGAP29)，它是 RhoA 的负调节因子。在诱导间充质转化的乳腺癌细胞中，ARHGAP29是32种GTP酶激活酶中唯一表达显着增加的酶。因此，我们研究了 ARHGAP29 的表达与 BC 中肿瘤进展之间是否存在相关性。由于他莫昔芬耐药 BC 细胞表现出间充质特性和侵袭性增加，我们还研究了 ARHGAP29 与他莫昔芬耐药中侵袭率增加之间的关系。问题是 ARHGAP29 是否是 BC 进展的合适预后标志物。组织微阵列用于研究 BC 和邻近正常乳腺组织中 ARHGAP29 的表达。使用 siRNA 进行敲低实验，研究 ARHGAP29 以及可能的下游因子 RhoC 和 pAKT1 对体外耐他莫昔芬 BC 球体侵袭性生长的影响。与邻近的正常乳腺组织相比，ARHGAP29 在 BC 组织中的表达经常增加。此外，有证据表明 ARHGAP29 高表达与晚期临床肿瘤分期之间存在相关性。与其亲代野生型细胞相比，他莫昔芬耐药的 BC 细胞显示出明显更高的 ARHGAP29 表达。在他莫昔芬耐药的 BC 细胞中敲低 ARHGAP29 后，RhoC 的表达显着降低。此外，pAKT1的表达显着降低。敲除 ARHGAP29 后，三维三苯氧胺抗性 BC 球体的侵袭性生长减少。 AKT1 激活剂 SC79 可以部分逆转这一情况。ARHGAP29 的表达与 BC 患者的临床肿瘤参数相关。此外，ARHGAP29 与他莫昔芬耐药 BC 细胞的侵袭性增加有关。 ARHGAP29 单独或与其下游伙伴 RhoC 和 pAKT1 组合可能成为 BC 进展的合适预后标志物。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

Aggressive breast cancer (BC) cells show high expression of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. In breast cancer cells in which mesenchymal transformation was induced, ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression increased significantly. Therefore, we investigated whether there is a correlation between expression of ARHGAP29 and tumor progression in BC. Since tamoxifen-resistant BC cells exhibit increased mesenchymal properties and invasiveness, we additionally investigated the relationship between ARHGAP29 and increased invasion rate in tamoxifen resistance. The question arises as to whether ARHGAP29 is a suitable prognostic marker for the progression of BC.Tissue microarrays were used to investigate expression of ARHGAP29 in BC and adjacent normal breast tissues. Knockdown experiments using siRNA were performed to investigate the influence of ARHGAP29 and the possible downstream actors RhoC and pAKT1 on invasive growth of tamoxifen-resistant BC spheroids in vitro.Expression of ARHGAP29 was frequently increased in BC tissues compared to adjacent normal breast tissues. In addition, there was evidence of a correlation between high ARHGAP29 expression and advanced clinical tumor stage. Tamoxifen-resistant BC cells show a significantly higher expression of ARHGAP29 compared to their parental wild-type cells. After knockdown of ARHGAP29 in tamoxifen-resistant BC cells, expression of RhoC was significantly reduced. Further, expression of pAKT1 decreased significantly. Invasive growth of three-dimensional tamoxifen-resistant BC spheroids was reduced after knockdown of ARHGAP29. This could be partially reversed by AKT1 activator SC79.Expression of ARHGAP29 correlates with the clinical tumor parameters of BC patients. In addition, ARHGAP29 is involved in increased invasiveness of tamoxifen-resistant BC cells. ARHGAP29 alone or in combination with its downstream partners RhoC and pAKT1 could be suitable prognostic markers for BC progression.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.