Smalley Tracess, Islam S M Anisul, Apostolatos Christopher, Apostolatos André, Acevedo-Duncan Mildred
Department of Chemistry, The University of South Florida, Tampa, FL 33620, USA.
Oncol Lett. 2019 Feb;17(2):1537-1546. doi: 10.3892/ol.2018.9792. Epub 2018 Dec 4.
It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma , invasive lobular carcinoma, ductal carcinoma and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.
据估计,2018年乳腺癌将成为女性癌症相关死亡的第二大主要原因。先前的研究表明,非典型蛋白激酶C-ζ(PKC-ζ)是乳腺癌中众多失调通路的一个组成部分,包括细胞增殖、存活和细胞周期上调。本研究调查了乳腺组织中的PKC-ζ蛋白,以评估其作为乳腺癌侵袭生物标志物的潜力,并证明PKC-ζ蛋白的过表达可指示致癌作用。本研究使用蛋白质印迹分析、免疫组织化学和统计分析(83个样本),分析了无肿瘤并发症个体以及恶性女性乳腺组织样本(小叶癌、浸润性小叶癌、导管癌和浸润性导管癌)中PKC-ζ的表达。本研究还通过Transwell侵袭试验和用于丝状肌动蛋白(F-肌动蛋白)组织的免疫荧光探针,评估了PKC-ζ敲低后MDA-MB-231乳腺癌细胞的侵袭行为。数据表明,与非侵袭组织相比,侵袭组织中PKC-ζ的表达更高。结果还表明,与小叶组织相比,导管组织中PKC-ζ含量更丰富。此外,蛋白质研究还表明,PKC-ζ是通过Ras相关C3肉毒杆菌毒素底物1(Rac1)和Ras同源基因家族成员A(RhoA)途径参与侵袭行为的一个组成部分,并且PKC-ζ是侵袭细胞中F-肌动蛋白重组所必需的。因此,PKC-ζ应被视为乳腺癌发展中的一个生物标志物以及侵袭性肿瘤细胞的一个指标。