Cytoplasmic expression of p21CIP1/WAF1 is correlated with IKKβ overexpression in human breast cancers
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Regulation of cytoplasmic p21CIP/WAF1 (p21) is of great clinical significance in molecular oncology due to its identification as an antiapoptotic factor, a poor survival predictor as well as a drug-resistance inducer. A retrospective study of the immunohistochemical (IHC) profiles of 128 human primary breast cancers showed that increased total and cytoplasmic p21 expression were highly associated with the expression of IκB kinase β (IKKβ), the major catalytic subunit of the IKK complex and another crucial player in tumorigenesis and drug resistance. The causal relationship study based on cultured cell lines, MDA-MB-453 and MCF-7, confirmed that IKKβ overexpression did upregulate protein levels of total and cytoplasmic p21. Mechanistic investigation demonstrated that IKKβ increased p21 expression through upregulation of p21 mRNA level. Moreover, by Western blotting, IKKβ was found to be able to upregulate Akt phosphorylation on Ser 473. This novel finding indicated that IKKβ could mediate cytoplasmic p21 accumulation via activation of its downstream target Akt, which was known to phosphorylate p21 and lead to cytoplasmic localization of p21.
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p21, when present within the nucleus, inhibits cell cycle progression, whereas upon phosphorylation it gets transported to the cytoplasm where it functions as an anti-apoptotic protein.
“p21WAF1/CIP1, when present within the nucleus, inhibits cell cycle progression, whereas upon phosphorylation it gets transported to the cytoplasm where it functions as an anti-apoptotic protein (Ping et al., 2006).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ping et al., 2006
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- Authors
- Ping, B., He, X., Xia, W., Lee, D.-F., Wei, Y., Yu, D., Mills, G., Shi, D., & Hung, M.-C.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Fudan University (CN)
- Corresponding author
- Hung, Mien-Chie
- Venue
- International Journal of Oncology
- Publisher
- Spandidos Publications
- Published
- 2006-11-01
- ISSN
- 1019-6439 (ISSN-L)
- 1791-2423
- OpenAlex
- W2586647371
- Cited by
- 7
- References
- 18
- Citations by year
- 2023: 1 · 2021: 1 · 2015: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Oncology (publishedVersion)
- Funders
- National Breast Cancer Foundation
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- p21, IκB kinase β, breast cancer, Akt phosphorylation, drug resistance, anti-apoptotic factors, MDA-MB-453, MCF-7 cells
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