TROP2 methylation and expression in tamoxifen-resistant breast cancer

Abstract

BackgroundThe DNA methyltransferase 1 inhibitor, 5-Aza-2′-deoxycytidine (5-Aza-dC) is a potential treatment for breast cancer. However, not all breast tumors will respond similarly to treatment with 5-Aza-dC, and little is known regarding the response of hormone-resistant breast cancers to 5-Aza-dC.MethodsWe demonstrate that 5-Aza-dC-treatment has a stronger effect on an estrogen receptor-negative, Tamoxifen-selected cell line, TMX2-28, than on the estrogen receptor-positive, MCF7, parental cell line. Using data obtained from the HM450 Methylation Bead Chip, pyrosequencing, and RT-qPCR, we identified a panel of genes that are silenced by promoter methylation in TMX2-28 and re-expressed after treatment with 5-Aza-dC.ResultsOne of the genes identified, tumor associated calcium signal transducer 2 (TACSTD2), is altered by DNA methylation, and there is evidence that in some cancers decreased expression may result in greater proliferation. Analysis of DNA methylation of TACSTD2 and protein expression of its product, trophoblast antigen protein 2 (TROP2), was extended to a panel of primary (n = 34) and recurrent (n = 34) breast tumors. Stratifying tumors by both recurrence and ER status showed no significant relationship between TROP2 levels and TACSTD2 methylation. Knocking down TACSTD2 expression in MCF7 increased proliferation however; re-expressing TACSTD2 in TMX2-28 did not inhibit proliferation, indicating that TACSTD2 re-expression alone was insufficient to explain the decreased proliferation observed after treatment with 5-Aza-dC.ConclusionsThese results illustrate the complexity of the TROP2 signaling network. However, TROP2 may be a valid therapeutic target for some cancers. Further studies are needed to identify biomarkers that indicate how TROP2 signaling affects tumor growth and whether targeting TROP2 would be beneficial to the patient.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0589-9) contains supplementary material, which is available to authorized users.

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas

“…Trophoblast cell surface antigen 2 has a conflicting biological role in different types of cancer, acting as either a tumor suppressor or an oncogene, as a reflex of its plasticity and complex signaling network (Zimmers et al., 2018). TROP2 is differentially expressed in several tissues, and recent meta‐analyses have linked its overexpression with poorer OS and DFS in various solid tumors (Xu et al., 2017; Zeng et al., 2016).…”

Trop2: Jack of All Trades, Master of None

“…Furthermore, knockdown of Trop2 in the cervical cancer cells promotes cell proliferation, migration, and invasion capabilities in vitro and enhances tumor growth capability in vivo [ 77 ]. In the MCF7 breast cancer cell line, knockdown of Trop2 slightly increases proliferation when compared to control cells [ 143 ]. The above-described findings suggest that the role of Trop2 in regulating proliferation is a complex, cell type-, and organ-specific phenomenon.…”

CORO1C is Associated With Poor Prognosis and Promotes Metastasis Through PI3K/AKT Pathway in Colorectal Cancer

“…Human trophoblast cell surface protein 2 (Trop2) is a cell-surface glycoprotein highly expressed in a variety of tumors, and the high expression of Trop2 protein is associated with poor survival prognosis of cancer patients ( Zhao et al, 2017 ; Zimmers et al, 2018 ; Sun et al, 2020 ). Trop2 plays a key role in inducing epithelial-mesenchymal transition (EMT) and regulating cell migration ( Li et al, 2017 ; Wu et al, 2017 ; Gu et al, 2018 ).…”