ArticlePloS one2007
Functional ablation of pRb activates Cdk2 and causes antiestrogen resistance in human breast cancer cells.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer.Frontiers in oncology · 2024Article
- Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.Molecular cancer research : MCR · 2023Article
- Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.The oncologist · 2022Review
- The Synergistic Effects of SHR6390 Combined With Pyrotinib on HER2+/HR+ Breast Cancer.Frontiers in cell and developmental biology · 2021Article
- Glucocorticoid receptor modulation decreases ER-positive breast cancer cell proliferation and suppresses wild-type and mutant ER chromatin association.Breast cancer research : BCR · 2019Article
- Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers.Breast cancer research : BCR · 2016Review
- Altered regulation of PDK4 expression promotes antiestrogen resistance in human breast cancer cells.SpringerPlus · 2015Article
- The other side of the coin: the tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND-CDK4/6-RB axis.Cell cycle (Georgetown, Tex.) · 2014Review
- Roscovitine confers tumor suppressive effect on therapy-resistant breast tumor cells.Breast cancer research : BCR · 2011Article
- Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer.Endocrine-related cancer · 2011Article
- Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells.British journal of cancer · 2010Article
- Biological determinants of endocrine resistance in breast cancer.Nature reviews. Cancer · 2009Review
- Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc.Molecular and cellular biology · 2009Article
- New insights into the functions and regulation of the transcriptional corepressors SMRT and N-CoR.Cell division · 2009Article
- Regulation of hormonal therapy resistance by cell cycle machinery.Gene therapy & molecular biology · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogens are required for the proliferation of hormone dependent breast cancer cells, making estrogen receptor (ER) positive tumors amenable to endocrine therapies such as antiestrogens. However, resistance to these agents remains a significant cause of treatment failure. We previously demonstrated that inactivation of the retinoblastoma protein (pRb) family tumor suppressors causes antiestrogen resistance in MCF-7 cells, a widely studied model of estrogen responsive human breast cancers. In this study, we investigate the mechanism by which pRb inactivation leads to antiestrogen resistance. Cdk4 and cdk2 are two key cell cycle regulators that can phosphorylate and inactivate pRb, therefore we tested whether these kinases are required in cells lacking pRb function. pRb family members were inactivated in MCF-7 cells by expressing polyomavirus large tumor antigen (PyLT), and cdk activity was inhibited using the cdk inhibitors p16(INK4A) and p21(Waf1/Cip1). Cdk4 activity was no longer required in cells lacking functional pRb, while cdk2 activity was required for proliferation in both the presence and absence of pRb function. Using inducible PyLT cell lines, we further demonstrated that pRb inactivation leads to increased cyclin A expression, cdk2 activation and proliferation in antiestrogen arrested cells. These results demonstrate that antiestrogens do not inhibit cdk2 activity or proliferation of MCF-7 cells in the absence of pRb family function, and suggest that antiestrogen resistant breast cancer cells resulting from pRb pathway inactivation would be susceptible to therapies that target cdk2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.