scholarly journals Endometrial cancer cell survival and apoptosis is regulated by protein kinase C α and δ

2006 ◽  
Vol 13 (4) ◽  
pp. 1251-1267 ◽  
Author(s):  
James M Haughian ◽  
Twila A Jackson ◽  
David M Koterwas ◽  
Andrew P Bradford
Keyword(s):  
Cell Death ◽  
Endometrial Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Endometrial Cancer Cell ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Induced Apoptosis

Endometrial cancer is the most common invasive gynecologic malignancy but the molecular mechanisms underlying its onset and progression are poorly understood. Paradoxically, endometrial tumors exhibit increased apoptosis, correlating with disease progression and poor patient prognosis. Endometrial tumors also show altered activity and expression of protein kinase C (PKC) isoforms, implicated in the regulation of programmed cell death; however, PKC modulation of apoptosis in endometrial cancer cells has not been investigated. We detected nine out of ten PKC isoforms in Ishikawa endometrial cancer cell lines, and demonstrated expression of both PKCα and δ in human endometrial tumors. To determine the functional roles of PKCα and δ in apoptosis in endometrial cancer, Ishikawa cells were treated with selective PKC inhibitors or adenoviral constructs encoding wild-type or isoform-specific, dominant-negative mutants. Apoptosis was assessed by DNA fragmentation and caspase-mediated poly-(ADP-ribose)-polymerase cleavage. The inhibition of PKCδ suppressed etoposide-induced apoptosis, while overexpression of PKCδ enhanced it. In contrast, inhibition of PKCα elevated basal levels of apoptosis and potentiated etoposide-induced cell death. Etoposide treatment also selectively activated PKCδ, but resulted in both cytosolic translocation and decreased activity of PKCα. A fraction of PKCδ also underwent caspase-dependent cleavage, in response to etoposide. Our results suggest that changes in apoptosis and PKC expression in endometrial cancer are mechanistically linked, such that PKCδ is required for DNA damage-induced apoptosis, while PKCα mediates a survival response. Thus, PKCα and δ expression and signaling may be important in endometrial tumorigenesis and could serve as potential prognostic indicators and/or novel targets for therapeutic intervention.

scholarly journals Protein kinase C alpha-dependent signaling mediates endometrial cancer cell growth and tumorigenesis

2009 ◽  
Vol 125 (11) ◽  
pp. 2556-2564 ◽  
Author(s):  
James M. Haughian ◽  
Elaine M. Reno ◽  
Alicia M. Thorne ◽  
Andrew P. Bradford
Keyword(s):  
Endometrial Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Growth ◽  
Cancer Cell ◽  
Cancer Cell Growth ◽  
Endometrial Cancer Cell ◽  
Kinase C ◽  
Protein Kinase C Alpha

scholarly journals Protein kinase C mediates platelet secretion and thrombus formation through protein kinase D2

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 416-424 ◽  
Author(s):  
Olga Konopatskaya ◽  
Sharon A. Matthews ◽  
Matthew T. Harper ◽  
Karen Gilio ◽  
Judith M. E. M. Cosemans ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Thrombus Formation ◽  
Dense Granule ◽  
Molecular Pathway ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Dense Granule Secretion ◽  
Granule Secretion

Abstract Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse in which 2 key phosphorylation sites in PKD2 have been mutated (Ser707Ala/Ser711Ala) show a significant reduction in agonist-induced dense granule secretion, but not in α-granule secretion. This deficiency in dense granule release was responsible for a reduced platelet aggregation and a marked reduction in thrombus formation. Our results show that in the molecular pathway to secretion, PKD2 is a key component of the PKC-mediated pathway to platelet activation and thrombus formation through its selective regulation of dense granule secretion.

scholarly journals Molecular Mechanisms of Protein Kinase C-induced Apoptosis in Prostate Cancer Cells

BMB Reports ◽  
2005 ◽  
Vol 38 (6) ◽  
pp. 639-645 ◽  
Author(s):  
Anatilde M. Gonzalez-Guerrico ◽  
John Meshki ◽  
Liqing Xiao ◽  
Fernando Benavides ◽  
Claudio J. Conti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Prostate Cancer Cells ◽  
Kinase C ◽  
Induced Apoptosis

Epidermal Growth Factor Activates Protein Kinase C in the Human Endometrial Cancer Cell Line HEC-1-A

1997 ◽  
Vol 67 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Patrick Connor ◽  
Francisco Talavera ◽  
Jae-Seong Kang ◽  
James Burke ◽  
James Roberts ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cancer Cell Line ◽  
Endometrial Cancer Cell ◽  
Kinase C ◽  
Epidermal Growth

2133-P: Protein Kinase C Delta Mediates Cytokine-Induced Apoptosis in the Pancreatic Beta Cell

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2133-P
Author(s):  
NIKKI L. FARNSWORTH ◽  
ROBERT A. PISCOPIO ◽  
RICHARD K. BENNINGER
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Protein Kinase C Delta ◽  
Kinase C ◽  
P Protein ◽  
Induced Apoptosis

scholarly journals Protein kinase C-independent stimulation of activator protein-1 and c-Jun N-terminal kinase activity in human endometrial cancer cells by the LHRH agonist triptorelin

2001 ◽  
pp. 651-658 ◽  
Author(s):  
C Grundker ◽  
L Schlotawa ◽  
V Viereck ◽  
G Emons
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Fold Increase ◽  
Lhrh Agonist ◽  
Activator Protein 1 ◽  
Kinase C ◽  
Lhrh Receptor

OBJECTIVE: The expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as a part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumours, including cancers of the endometrium. The signalling pathway through which LHRH acts in endometrial cancer is distinct from that in pituitary gonadotrophs. The LHRH receptor interacts with the mitogenic signal transduction of growth factor receptors via activation of a phosphotyrosine phosphatase, resulting in down-regulation of cancer cell proliferation. In addition, LHRH activates nucleus factor kappaB (NFkappaB) and protects the cancer cells from apoptosis. This study was conducted to investigate additional signalling mechanisms of the LHRH receptor cooperating with NFkappaB in endometrial cancer cells. DESIGN: The LHRH agonist triptorelin-induced activator protein-1 (AP-1) activation was analysed using a pAP-1-SEAP reporter gene assay. Expression of c-jun mRNA was quantified using quantitative reverse transcription (RT)-PCR. c-Jun N-terminal kinase (JNK) activity was measured by quantification of phosphorylated c-Jun protein. RESULTS: Treatment of Ishikawa and Hec-1A human endometrial cancer cells with 100 nM triptorelin resulted in a 3.1-fold and 3.5-fold activation of AP-1 respectively (P<0.05). If the cells had been made quiescent, treatment with triptorelin (100 nM) resulted in a 41.7-fold and 48.6-fold increase of AP-1 activation respectively (P<0.001). This effect was completely blocked by simultaneous treatment with pertussis toxin (PTX). A 17.6-fold and 17.3-fold increase of c-jun mRNA expression respectively (P<0.001) was obtained after 20 min of stimulation with triptorelin (100 nM). Treatment with 1 nM triptorelin resulted in a 12.5-fold or an 11.9-fold increase, and treatment with 10 pM triptorelin resulted in a 6.5-fold or a 5.2-fold increase of maximal c-jun mRNA expression respectively (P<0.001). Maximal c-Jun phosphorylation (68.5-fold and 60.2-fold, respectively, P<0.001) was obtained after 90 min incubation with triptorelin (100 nM). CONCLUSIONS: These results suggest that the LHRH agonist triptorelin stimulates the activity of AP-1 in human endometrial cancer cells mediated through PTX-sensitive G-protein alphai. In addition, triptorelin activates JNK, known to activate AP-1. In earlier investigations we have shown that triptorelin does not activate phospholipase and protein kinase C (PKC) in endometrial cancer cells. In addition, it has been demonstrated that triptorelin inhibits growth factor-induced mitogen activated protein kinase (MAPK, ERK) activity. Thus triptorelin-induced activation of the JNK/AP-1 pathway in endometrial cancer cells is independent of the known AP-1 activators, PKC or MAPK (ERK).

scholarly journals Nanog expression is negatively regulated by protein kinase C activities in human cancer cell lines

2013 ◽  
Vol 34 (7) ◽  
pp. 1497-1509 ◽  
Author(s):  
Wing-Keung Chu ◽  
Pei-Min Dai ◽  
Hsin-Lun Li ◽  
Chia-Chu Pao ◽  
Jan-Kan Chen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Nanog Expression ◽  
Kinase C
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