Tamoxifen is widely used as a highly effective drug for treating estrogen‑receptor (ER) alpha‑positive breast cancer. However, tamoxifen resistance developed during cancer treatment remains a significant challenge. Tongue cancer resistance‑related protein1 (TCRP1), which is recognized as a novel drug target, is related to chemo‑resistance in human cancers, moreover, it is often overexpressed in various cancer cells, such as in lung cancer, breast cancer, and tongue cancer. However, the effects of TCRP1 on tamoxifen‑resistant breast cancer cells and tissues are far from clear. The present study revealed that TCRP1 induced tamoxifen resistance in breast cancer cells. Western blotting, quantitative real‑time polymerase chain reaction (RT‑PCR) and immunohistochemical staining were performed to detect the expression level of TCRP1 in vivo and in vitro between primary breast cancer tissues and tamoxifen‑resistant breast cancer tissues. The data revealed that the expression of TCRP1 was upregulated in the tamoxifen‑resistant breast cancer tissues and human breast cancer cell line, MCF‑7. Further study revealed that knocking down TCRP1 inhibited the growth of MCF‑7 cells with tamoxifen‑resistance (MCF7‑R cells) and induced cell apoptosis. Moreover, TCRP1 promoted serum‑ and glucocorticoid‑inducible kinase 1 (SGK1) activation via phosphorylation of phosphoinositide‑dependent kinase 1 (PDK1) in MCF7‑R cells. In addition, it was also observed that knocking down TCRP1 inhibited tumorigenesis of MCF‑7 cells in nude mice. In conclusion, these data indicated that TCRP1 could induce tamoxifen resistance by regulating the PDK1/SGK1 signaling pathway. Thus, TCRP1 could be explored as a promising candidate for treating tamoxifen‑resistant breast cancer in the future.
Keywords: breast cancer; tamoxifen-resistant; tongue cancer resistance-related protein1; glucocorticoid-inducible kinase 1; MCF-7 cells.