Tamoxifen-resistant breast cancer cells possess cancer stem-like cell properties / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis. Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy. Although acquired resistance to endocrine treatment has been extensively studied, the underlying mechanisms are unclear. We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy. Therefore, we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.</p><p><b>METHODS</b>Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively. Stem-cell markers (SOX-2, OCT-4, and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR. Morphological observation was performed to characterize EMT.</p><p><b>RESULTS</b>After induction of TAM resistance, TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P < 0.05), indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells. TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P < 0.01), demonstrating the elevated CSC properties of TAM-R MCF7 cells. Consistently, qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2, OCT-4, and CD133, compared to those of WT MCF7 cells (P < 0.05). Morphologically, TAM-R MCF7 cells showed a fibroblastic phenotype, but WT MCF7 cells were epithelial-like. After induction of TAM resistance, qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail, vimentin, and N-cadherin and decreased levels of E-cadherin, which are considered as EMT characteristics (P < 0.05).</p><p><b>CONCLUSION</b>TAM-R MCF7 cells possess CSC characteristics and may be responsible for TAM resistance during breast cancer therapy.</p>

Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

OBJECTIVE@#To analyze breast cancer bone metastasis related gene-CXCR4.@*METHODS@#This research screened breast cancer bone metastasis related genes by high-flux gene chip.@*RESULTS@#It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis.@*CONCLUSIONS@#The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.