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Article: Cyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27Kip1 Association with Cyclin E-Cdk2

TitleCyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27<sup>Kip1</sup> Association with Cyclin E-Cdk2
Authors
Issue Date2001
Citation
Journal of Biological Chemistry, 2001, v. 276, n. 50, p. 47675-47683 How to Cite?
AbstractLong-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 Identifierhttp://hdl.handle.net/10722/326446
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMusgrove, Elizabeth A.-
dc.contributor.authorHunter, Lisa Jane K.-
dc.contributor.authorLee, Christine S.L.-
dc.contributor.authorSwarbrick, Alexander-
dc.contributor.authorHui, Rina-
dc.contributor.authorSutherland, Robert L.-
dc.date.accessioned2023-03-10T02:19:20Z-
dc.date.available2023-03-10T02:19:20Z-
dc.date.issued2001-
dc.identifier.citationJournal of Biological Chemistry, 2001, v. 276, n. 50, p. 47675-47683-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/326446-
dc.description.abstractLong-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.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleCyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27<sup>Kip1</sup> Association with Cyclin E-Cdk2-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M106371200-
dc.identifier.pmid11590147-
dc.identifier.scopuseid_2-s2.0-0035861565-
dc.identifier.volume276-
dc.identifier.issue50-
dc.identifier.spage47675-
dc.identifier.epage47683-
dc.identifier.isiWOS:000172768500130-

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