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- Publisher Website: 10.1074/jbc.M106371200
- Scopus: eid_2-s2.0-0035861565
- PMID: 11590147
- WOS: WOS:000172768500130
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Article: Cyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27Kip1 Association with Cyclin E-Cdk2
Title | Cyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27<sup>Kip1</sup> Association with Cyclin E-Cdk2 |
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Authors | |
Issue Date | 2001 |
Citation | Journal of Biological Chemistry, 2001, v. 276, n. 50, p. 47675-47683 How to Cite? |
Abstract | Long-term growth inhibition, arrest in G1 phase and reduced activity of both cyclin D1-Cdk4 and cyclin E-Cdk2 are elicited by progestin treatment of breast cancer cells in culture. Decreased cyclin expression, induction of p18INK4c and increased association of the CDK inhibitors p21WAF1/Cip1 and p27Kip1 with cyclin E-Cdk2 have been implicated in these responses. To determine the role of decreased cyclin expression, T-47D human breast cancer cells constitutively expressing cyclin D1 or cyclin E were treated with the progestin ORG 2058. Overexpression of cyclin E had only a modest effect on growth inhibition. Although cyclin E expression was maintained during progestin treatment, cyclin E-Cdk2 activity decreased by ∼60%. This was accompanied by p27Kip1 association with cyclin E-Cdk2, indicating that both cyclin E down-regulation and p27 Kip1 recruitment contribute to the decrease in activity. In contrast, overexpression of cyclin D1 induced progestin resistance and cell proliferation continued despite decreased cyclin E-Cdk2 activity. Progestin treatment of cyclin D1-overexpressing cells was associated with increased p27Kip1 association with cyclin E-Cdk2. Thus the ability of cyclin D1 to confer progestin resistance does not depend on sequestration of p27 Kip1 away from cyclin E-Cdk2, providing evidence for a critical function of cyclin D1 other than as a high-capacity "sink" for p27Kip1. These data indicate that regulation of cyclin D1 is a critical element of progestin inhibition in breast cancer cells and suggest that breast cancers overexpressing cyclin D1 may respond poorly to progestin therapy. |
Persistent Identifier | http://hdl.handle.net/10722/326446 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Musgrove, Elizabeth A. | - |
dc.contributor.author | Hunter, Lisa Jane K. | - |
dc.contributor.author | Lee, Christine S.L. | - |
dc.contributor.author | Swarbrick, Alexander | - |
dc.contributor.author | Hui, Rina | - |
dc.contributor.author | Sutherland, Robert L. | - |
dc.date.accessioned | 2023-03-10T02:19:20Z | - |
dc.date.available | 2023-03-10T02:19:20Z | - |
dc.date.issued | 2001 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2001, v. 276, n. 50, p. 47675-47683 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10722/326446 | - |
dc.description.abstract | Long-term growth inhibition, arrest in G1 phase and reduced activity of both cyclin D1-Cdk4 and cyclin E-Cdk2 are elicited by progestin treatment of breast cancer cells in culture. Decreased cyclin expression, induction of p18INK4c and increased association of the CDK inhibitors p21WAF1/Cip1 and p27Kip1 with cyclin E-Cdk2 have been implicated in these responses. To determine the role of decreased cyclin expression, T-47D human breast cancer cells constitutively expressing cyclin D1 or cyclin E were treated with the progestin ORG 2058. Overexpression of cyclin E had only a modest effect on growth inhibition. Although cyclin E expression was maintained during progestin treatment, cyclin E-Cdk2 activity decreased by ∼60%. This was accompanied by p27Kip1 association with cyclin E-Cdk2, indicating that both cyclin E down-regulation and p27 Kip1 recruitment contribute to the decrease in activity. In contrast, overexpression of cyclin D1 induced progestin resistance and cell proliferation continued despite decreased cyclin E-Cdk2 activity. Progestin treatment of cyclin D1-overexpressing cells was associated with increased p27Kip1 association with cyclin E-Cdk2. Thus the ability of cyclin D1 to confer progestin resistance does not depend on sequestration of p27 Kip1 away from cyclin E-Cdk2, providing evidence for a critical function of cyclin D1 other than as a high-capacity "sink" for p27Kip1. These data indicate that regulation of cyclin D1 is a critical element of progestin inhibition in breast cancer cells and suggest that breast cancers overexpressing cyclin D1 may respond poorly to progestin therapy. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Biological Chemistry | - |
dc.title | Cyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27<sup>Kip1</sup> Association with Cyclin E-Cdk2 | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1074/jbc.M106371200 | - |
dc.identifier.pmid | 11590147 | - |
dc.identifier.scopus | eid_2-s2.0-0035861565 | - |
dc.identifier.volume | 276 | - |
dc.identifier.issue | 50 | - |
dc.identifier.spage | 47675 | - |
dc.identifier.epage | 47683 | - |
dc.identifier.isi | WOS:000172768500130 | - |