Lubovac-Pilav Zelmina, Borràs Daniel M, Ponce Esmeralda, Louie Maggie C
Systems Biology Research Centre - Bioinformatics, School of Bioscience, University of Skövde, Skövde, Sweden.
Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, California, United States of America.
PLoS One. 2013 Dec 20;8(12):e84646. doi: 10.1371/journal.pone.0084646. eCollection 2013.
Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.
镉是一种金属雌激素,已知其可激活雌激素受体并促进乳腺癌细胞生长。先前的研究表明镉与更恶性肿瘤的发生有关;然而,镉诱导恶性肿瘤背后的分子机制仍不清楚。本研究使用将乳腺癌细胞暴露于镉超过6个月所衍生的克隆细胞系(MCF-7-Cd4、-Cd6、-Cd7、-Cd8和-Cd12),旨在识别与慢性镉暴露相关的基因表达特征。我们的结果表明,长期镉暴露不仅会导致基因失调,实际上还会导致一种独特的表达谱。在镉暴露细胞中失调的基因涉及多个生物学过程(如细胞生长、凋亡等)和分子功能(如镉/金属离子结合、转录因子活性等)。层次聚类表明,五个克隆镉细胞系共享与乳腺癌相关基因的共同基因表达特征,明显区分了对照细胞和镉暴露细胞。本研究结果为镉对乳腺癌的细胞和分子影响提供了见解,并强调了研究慢性镉暴露作为促进乳腺癌进展的一种可能机制的重要性。