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.

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de Vente, James E.; Kukoly, Cynthia A.; Bryant, Winifred O.; Posekany, Karla J.; Chen, Jianming; Fletcher, Donald J.; Parker, Peter J.; Pettit, George J.; Lozano, Guillermina; Cook, Paul P.; Ways, D. Kirk
Abstract
Protein 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 1995
URI
http://hdl.handle.net/10342/3254
Subject
 Protein kinase C; Phorbol esters; Breast--Cancer; Apoptosis; p53 
Date
1995-10
Citation:
APA:
de Vente, James E., & Kukoly, Cynthia A., & Bryant, Winifred O., & Posekany, Karla J., & Chen, Jianming, & Fletcher, Donald J., & Parker, Peter J., & Pettit, George J., & Lozano, Guillermina, & Cook, Paul P., & Ways, D. Kirk. (October 1995). 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.. , (. Retrieved from http://hdl.handle.net/10342/3254

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MLA:
de Vente, James E., and Kukoly, Cynthia A., and Bryant, Winifred O., and Posekany, Karla J., and Chen, Jianming, and Fletcher, Donald J., and Parker, Peter J., and Pettit, George J., and Lozano, Guillermina, and Cook, Paul P., and Ways, D. Kirk. "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.". . . (.), October 1995. October 27, 2020. http://hdl.handle.net/10342/3254.
Chicago:
de Vente, James E. and Kukoly, Cynthia A. and Bryant, Winifred O. and Posekany, Karla J. and Chen, Jianming and Fletcher, Donald J. and Parker, Peter J. and Pettit, George J. and Lozano, Guillermina and Cook, Paul P. and Ways, D. Kirk, "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.,"  , no. (October 1995), http://hdl.handle.net/10342/3254 (accessed October 27, 2020).
AMA:
de Vente, James E., Kukoly, Cynthia A., Bryant, Winifred O., Posekany, Karla J., Chen, Jianming, Fletcher, Donald J., Parker, Peter J., Pettit, George J., Lozano, Guillermina, Cook, Paul P., Ways, D. Kirk. 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.. . October 1995; () . http://hdl.handle.net/10342/3254. Accessed October 27, 2020.
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East Carolina University