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Id-1 regulates Bcl-2 and Bax expression through p53 and NF-κB in MCF-7 breast cancer cells

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Abstract

Although increasing evidence supports the protective role of inhibitor of differentiation and DNA binding-1 (Id-1) against anticancer drug-induced apoptosis, the underlying molecular mechanisms seem to vary depending on the tumor system. Here, we examined the direct role of Id-1 in MCF-7 breast cancer cells by ectopically overexpressing Id-1 under serum-free condition, where the endogenous Id-1 expression was suppressed. Id-1 expression resulted in increased number of viable cells, reduced Bax expression, enhanced Bcl-2 expression, but no change in Bcl-xL expression. The expression of nuclear factor-κB (NF-κB) was augmented, while those of p53 and IκB were reduced. Such changes in p53 and NF-κB pathways were also functional, as assessed by real-time polymerase chain reactions and reporter assays of their known downstream targets, p21 and Il-6, as well as Bax and Bcl-2 genes. Finally, Id-1 played a protective role against taxol-induced apoptosis in breast cancer cells as assessed by MTT assay and apoptotic cell count upon taxol treatment (0–200 nM). Reduced Bax expression and enhanced Bcl-2 expression by Id-1 were also noted in the presence of taxol. Taken together, we present a molecular mechanism where Id-1 regulates p53 and NF-κB pathways, which in turn regulates Bax and Bcl-2 genes, thus providing a survival advantage under exogenous stress such as serum-free or taxol treatment in MCF-7 breast cancer cells. In this regard, inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of breast cancer progression and anti-cancer drug resistance.

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Acknowledgements

This work was supported by the Korea Research Foundation Grant (KRF-2007-314-E00041) funded by the Korean Government (MOEHRD, Basic Research Promotion Fund).

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Republic of Korea

    Hwan Kim, Heekyoung Chung, Hyun-Jun Kim, Jeong-Yeon Lee, Mi-Yun Oh & Gu Kong

  2. Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Republic of Korea

    Yongseok Kim

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  1. Hwan Kim
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Correspondence to Gu Kong.

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Hwan Kim and Heekyoung Chung equally contributed to this work.

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Kim, H., Chung, H., Kim, HJ. et al. Id-1 regulates Bcl-2 and Bax expression through p53 and NF-κB in MCF-7 breast cancer cells. Breast Cancer Res Treat 112, 287–296 (2008). https://doi.org/10.1007/s10549-007-9871-6

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  • DOI: https://doi.org/10.1007/s10549-007-9871-6

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