ArticleBreast cancer research : BCR2003
Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis.
Article in Breast cancer research : BCR, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 104 citations in OpenAlex.
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- p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.International journal of molecular sciences · 2024Article
- BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21International journal of biological sciences · 2024Article
- Cellular senescence in cancer: clinical detection and prognostic implications.Journal of experimental & clinical cancer research : CR · 2022Review
- Sustained Supratherapeutic Paclitaxel Delivery Enhances Irreversible Sarcoma Cell Death.Molecular cancer therapeutics · 2022Article
- Cyclin-dependent kinase inhibitors in malignant hematopoiesis.Frontiers in oncology · 2022Review
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- Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition.Scientific reports · 2019Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- p21cip1/waf1 Coordinate Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress.Cancers · 2019Review
- An integrated stress response via PKR suppresses HER2+ cancers and improves trastuzumab therapy.Nature communications · 2019Article
- The role of p21/CIP1/WAF1 (p21) in the negative regulation of the growth hormone/growth hormone receptor and epidermal growth factor/epidermal growth factor receptor pathways, in growth hormone transduction defect.Annals of pediatric endocrinology & metabolism · 2018Article
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- Mechanistic added value of a trans-Sulfonamide-Platinum-Complex in human melanoma cell lines and synergism with cis-Platin.Molecular cancer · 2017Article
- The KIP/CIP family members p21^{Waf1/Cip1} and p57^{Kip2} as diagnostic markers for breast cancer.Cancer biomarkers : section A of Disease markers · 2017Article
- Article
- Review
- Expression of CDKN1A/p21 and TGFBR2 in breast cancer and their prognostic significance.International journal of clinical and experimental pathology · 2015Article
- Verrucarin A alters cell-cycle regulatory proteins and induces apoptosis through reactive oxygen species-dependent p38MAPK activation in the human breast cancer cell line MCF-7.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer.Breast cancer research and treatment · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER-2 (c-erbB2/Neu) predicts the prognosis of and may influence treatment responses in breast cancer. HER-2 activity induces the cytoplasmic location of p21WAFI/CIPI in cell culture, accompanied by resistance to apoptosis. p21WAFI/CIPI is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest in association with nuclear localisation of p21WAFI/CIPI. We previously showed that higher levels of cytoplasmic p21WAFI/CIPI in breast cancers predicted reduced survival at 5 years. The present study examined HER-2 and p21WAFI/CIPI expression in a series of breast cancers with up to 9 years of follow-up, to evaluate whether in vitro findings were related to clinical data and the effect on outcome.
methodsThe CB11 anti-HER2 monoclonal antibody and the DAKO Envision Plus system were used to evaluate HER-2 expression in 73 patients. p21WAFI/CIPI staining was performed as described previously using the mouse monoclonal antibody Ab-1 (Calbiochem, Cambridge, MA, USA).
resultsHER-2 was evaluable in 67 patients and was expressed in 19% of cases, predicting reduced overall survival (P = 0.02) and reduced relapse-free survival (P = 0.004; Cox regression model). HER-2-positive tumours showed proportionately higher cytoplasmic p21WAFI/CIPI staining using an intensity distribution score (median, 95) compared with HER-2-negative cancers (median, 47) (P = 0.005). There was a much weaker association between nuclear p21WAFI/CIPI and HER-2 expression (P = 0.05), suggesting an inverse relationship between nuclear p21WAF1/CIP1 and HER-2.
conclusionThis study highlights a new pathway by which HER-2 may modify cancer behaviour. HER-2 as a predictor of poor prognosis may partly relate to its ability to influence the relocalisation of p21WAFI/CIPI from the nucleus to the cytoplasm, resulting in a loss of p21WAFI/CIPItumour suppressor functions. Cytoplasmic p21WAFI/CIPI may be a surrogate marker of functional HER-2 in vivo.
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