Tan Ruizhi, Wang Li, Song Jie, Li Jianchun, He Tao
Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
The Institute for Cancer Medicine, Research Center for Preclinical Medicine and College of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.
J Cancer Res Ther. 2017;13(4):707-714. doi: 10.4103/jcrt.JCRT_1396_16.
Breast cancer is one of the most common malignancies in women, and the tumor cells' invasion and metastasis is the main cause of death. Recent reports showed that Twist, a transcription factor, plays multiple roles in breast cancer initiation, progress, and metastasis. However, the underlying mechanisms of Twist in tumor invasion and metastasis of breast cancer still remain unclear. Here, we examined the correlation between Twist, E-cadherin, and estrogen receptor (ER) in promoting invasion and metastasis in breast cancer cells and tissues.
The mRNA and protein expression of Twist, E-cadherin, and ER in breast cancer cell lines (MCF-7, MDA-MB-435, MDA-MB-231, and ZR-75-30) and human invasive ductal carcinoma (IDC) tissues from 32 patients were detected by reverse transcription-polymerase chain reaction and immunohistochemistry (IHC), respectively.
Expression of Twist in cells with high ability of invasion and metastasis was higher than that in MCF-7 cell line which has low ability of invasion and metastasis, while the expression of ER and E-cadherin was much more higher in MCF-7 cell line than in other cells. IHC showed that the expression rate of Twist in IDC tissues and adjacent tissues was 84.38% and 31.25% and the positive expression of E-cadherin and ER was 21.88% and 40.63% in IDC tissues and 81.25% and 84.38% in adjacent tissues, respectively. Interestingly, overexpression of Twist promoted cellular invasion and metastasis and decreased the expression of E-cadherin, ER, AKT, and p-AKT in HEK-293 cells.
Taken together, these findings demonstrated that Twist was upregulated in high invasion and metastasis cell lines as well as IDC tissues companioned with downregulated expression of E-cadherin and ER, which provides important clues for the deeper study of breast cancer.
乳腺癌是女性最常见的恶性肿瘤之一,肿瘤细胞的侵袭和转移是主要的死亡原因。最近的报告显示,转录因子Twist在乳腺癌的发生、发展和转移中发挥多种作用。然而,Twist在乳腺癌肿瘤侵袭和转移中的潜在机制仍不清楚。在此,我们研究了Twist、E-钙黏蛋白和雌激素受体(ER)在促进乳腺癌细胞和组织侵袭和转移中的相关性。
分别采用逆转录-聚合酶链反应和免疫组织化学(IHC)检测乳腺癌细胞系(MCF-7、MDA-MB-435、MDA-MB-231和ZR-75-30)以及32例患者的人浸润性导管癌(IDC)组织中Twist、E-钙黏蛋白和ER的mRNA和蛋白表达。
侵袭和转移能力强的细胞中Twist的表达高于侵袭和转移能力弱的MCF-7细胞系,而MCF-7细胞系中ER和E-钙黏蛋白的表达远高于其他细胞。免疫组织化学显示,IDC组织和癌旁组织中Twist的表达率分别为84.38%和31.25%,IDC组织中E-钙黏蛋白和ER阳性表达率分别为21.88%和40.63%,癌旁组织中分别为81.25%和84.38%。有趣的是,Twist的过表达促进了HEK-293细胞的侵袭和转移,并降低了E-钙黏蛋白、ER、AKT和p-AKT的表达。
综上所述,这些发现表明,在高侵袭和转移细胞系以及IDC组织中Twist上调,同时伴有E-钙黏蛋白和ER表达下调,这为深入研究乳腺癌提供了重要线索。