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Endocrine, paracrine and intracrine mechanisms of growth regulation in normal and malignant breast epithelium
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
J. R. Pasqualini, G. S. Chetrite
Studies on estrogen metabolism have demonstrated that 17ß-HSD type I reductive activity is very high in hormone-dependent breast cancer cells (MCF-7, T-47D), whereas in hormone-independent cells (MDA-MB-231, MDA-MB-468) the oxidative activity is preferential54,55, suggesting that there is a change in 17ß-HSD phenotype in neoplastic cells.
2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Environmental Antiestrogens:Characterization and Mechanism of Action
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
The antiestrogenic activities of AhR agonists have primarily been investigated in E2-responsive human breast cancer cell lines, and most studies have demonstrated a correlation between Ah- and E2-responsiveness. These results suggest that the potential clinical utility of AhR agonists for treatment of breast cancer would be limited to ER-positive tumors. However, after screening a number of ER-negative breast cancer cell lines, it was shown that ER-negative MDA-MB-468 cells expressed the AhR, and TCDD induced CYP1A1 gene expression, ethoxyresorufin O-deethylase (EROD) activity, and CAT activity in cells transiently transfected with pRNH11c. These data established MDA-MB-468 cells as the first ER-negative Ah-responsive breast cancer cell line. Previous studies showed that cytotoxic drugs and EGF inhibited growth of MDA-MB-468 cells, and the unusual antimitogenic activity of EGF was accompanied by increased expression of EGF receptor, c-myc and c-fos protooncogene levels, and increased apoptosis. TCDD also significantly decreased growth of MDA-MB-468 cells and increased EGF receptor mRNA levels; however, TCDD did not induce c-fos or myc gene expression and was significantly less active than EGF as an inducer of apoptosis. EGF protein and mRNA levels are expressed at low levels in this cell line, and TCDD did not significantly modulate this response. Subsequent studies showed that TCDD increased TGFα mRNA and immunoreactive protein levels in MDA-MB-468 cells, and antibodies directed against the EGF receptor blocked the antimitogenic activity of TCDD. Since TGFα protein alone also inhibited proliferation of MDA-MB-468 cells, the results of this study showed that the antimitogenic activity of TCDD in this ER-negative cell line was associated with induction of TGFα protein. These data illustrate the unusual breast cancer cell-specific antimitogenic activity of TCDD, which inhibits TGFα and growth factor-induced proliferation of ER-positive breast cancer cells (Figure 8.4) but induces TGFα protein, which is antimitogenic in ER-negative MDA-MB-468 cells.
A HER2-targeted antibody-novel DNA topoisomerase I inhibitor conjugate induces durable adaptive antitumor immunity by activating dendritic cells
Published in mAbs, 2023
Xiaoding Tan, Peng Fang, Kaiying Li, Meng You, Yuxia Cao, Hui Xu, Xiaohong Zhu, Lu Wang, Xin Wei, Haiying Wen, Wendi Li, Lei Shi, Xiaowei Sun, Dongan Yu, Huikai Zhu, Zhenzhen Wang, Datao Liu, Hui Shen, Wei Zhou, Maomao An
The following cells lines were purchased from the American Type Culture Collection: human breast cancer cell lines BT474 and SK-BR-3, human gastric cancer cell line NCI-N87, human pancreatic cancer cell line BxPC-3, mouse colon cancer cell line CT26.WT, and mouse breast cancer cell line EMT6. Cells were cultured in appropriate media containing 10% fetal bovine serum (FBS). Human breast cancer cell line MDA-MB-468 was purchased from the National Collection of Authenticated Cell Cultures of Chinese Academy of Sciences and cultured in medium containing 10% FBS. CT26.WT-HER2, a cell line stably transfected with the full-length human HER2 gene, was purchased from BYinno Biotechnology Co., Ltd. and cultured in Dulbecco’s modified eagle medium containing 10% FBS and 20 μg/mL puromycin (Gibco, Cat# 15070–063). The dendritic cells were purchased from Milestone (Shanghai) Biological Science & Technology Co. Ltd. and the informed consent for the scientific research in this study was obtained from the dendritic cells’ donors.
Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation
Published in Nutrition and Cancer, 2021
Marjorie Anne A. Layosa, Nara N. Lage, Boon P. Chew, Liezl Atienza, Susanne Mertens-Talcott, Stephen Talcott, Giuliana D. Noratto
Besides the anthocyanins, other phenolic compounds present in DSC [e.g., hydroxycinnamic acids, flavonols, flavanols (16)] have shown chemopreventive/therapeutic activities in breast and other cancer types. Quercetin-induced apoptosis and cell cycle arrest in MDA-MB-453 cells through downregulation of anti-apoptotic Bcl-2, and the upregulation of pro-apoptotic biomarkers Bax, cytochrome c, cleaved caspase-3, and PARP-1 (29). Epigallocatechin-3-gallate (EGCG) induced apoptosis in a dose-dependent manner through upregulation of caspase-3 and -9 cleavage and Bax in T47D ER+ breast cancer cells at similar extent than the chemotherapeutic drug tamoxifen (30). It also inhibited MDA-MB-468 ER- breast cancer cells through Bax/Bcl-2 ratio upregulation, cytochrome c release, cleavage of caspase-3 and PARP-1, and DNA and nuclei fragmentation (31). Likewise, extracts containing a mixture of phenolic acids and flavonols (3-p-coumaroylquinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside) induced PARP-1 cleavage and downregulated anti-apoptotic Bcl-2 expression in triple negative MDA-MB-231 breast cancer cell (32).
A novel role for an old target: CD45 for breast cancer immunotherapy
Published in OncoImmunology, 2021
Annat Raiter, Oran Zlotnik, Julia Lipovetsky, Shany Mugami, Shira Dar, Ido Lubin, Eran Sharon, Cyrille J. Cohen, Rinat Yerushalmi
MDA-MB-231 and MDA-MB-468 (obtained from ATCC, Biological Industries, Kibbutz Beit Ha Emek, Israel) is a human triple-negative breast cancer cell line that is Her2-neu, estrogen receptor (ER)- and progesterone receptor (PR)-negative. MCF-10A (obtained from ATCC) are normal breast cells. Cells were grown in DMEM supplemented with 10% FCS, l-glutamine (2 mM), Na-pyruvate (1 nM), penicillin (100 μ/ml), streptomycin sulfate (0.1 mg/ml) and nystatine (12.5 μ/ml) complete culture medium (Biological Industries). Cultures were maintained at 37°C in a humidified 5% CO2 incubator. A large stock of cells was prepared to maintain homogeneity and tumorigenicity of the cell line. Cells were not used beyond passage five and examined for mycoplasma (Mycoplasma detection kit, Biological Industries) at least once every six months.