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Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.

dc.contributor.authorde Vente, James E.en_US
dc.contributor.authorKukoly, Cynthia A.en_US
dc.contributor.authorBryant, Winifred O.en_US
dc.contributor.authorPosekany, Karla J.en_US
dc.contributor.authorChen, Jianmingen_US
dc.contributor.authorFletcher, Donald J.en_US
dc.contributor.authorParker, Peter J.en_US
dc.contributor.authorPettit, George J.en_US
dc.contributor.authorLozano, Guillerminaen_US
dc.contributor.authorCook, Paul P.en_US
dc.contributor.authorWays, D. Kirken_US
dc.date.accessioned2011-02-17T16:48:34Zen_US
dc.date.accessioned2011-05-17T00:25:40Z
dc.date.available2011-02-17T16:48:34Zen_US
dc.date.available2011-05-17T00:25:40Z
dc.date.issued1995-10en_US
dc.description.abstractProtein kinase C (PKC) modulates growth, differentiation, and apoptosis in a cell-specific fashion. Overexpression of PKC-a in MCF-7 breast cancer cells (MCF-7-PKC-a cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-c cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G, arrest that was accompanied by Cipl expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-a cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-a cells that waned at higher concentrations. TPA-treated MCF-7-PKC-a cells accumulated in G2/M, did not express p53, displayed decreased Cipl expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-a cells expressed gadd45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression ofgadd45 in a p53-independent fashion. Originally published Journal of Clinical Investigation, Vol. 96, No. 4, Oct 1995en_US
dc.identifier.citationJournal of Clinical Investigation; 96:4 p. 1874-1886en_US
dc.identifier.pmidPMC185824en_US
dc.identifier.urihttp://hdl.handle.net/10342/3254en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://www.jci.org/archiveen_US
dc.rightsAuthor notified of opt-out rights by Cammie Jennings prior to upload of this article.en_US
dc.subjectProtein kinase Cen_US
dc.subjectPhorbol estersen_US
dc.subjectBreast--Canceren_US
dc.subjectApoptosisen_US
dc.subjectp53en_US
dc.titlePhorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.en_US
dc.typeArticleen_US

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