scholarly journals Overexpression of Protein Kinase C βII Induces Colonic Hyperproliferation and Increased Sensitivity to Colon Carcinogenesis

1999 ◽  
Vol 145 (4) ◽  
pp. 699-711 ◽  
Author(s):  
Nicole R. Murray ◽  
Laurie A. Davidson ◽  
Robert S. Chapkin ◽  
W. Clay Gustafson ◽  
Diane G. Schattenberg ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Intestinal Epithelium ◽  
Glycogen Synthase ◽  
Colon Carcinogenesis ◽  
Aberrant Crypt Foci ◽  
Preneoplastic Lesions ◽  
Kinase C

Protein kinase C βII (PKC βII) has been implicated in proliferation of the intestinal epithelium. To investigate PKC βII function in vivo, we generated transgenic mice that overexpress PKC βII in the intestinal epithelium. Transgenic PKC βII mice exhibit hyperproliferation of the colonic epithelium and an increased susceptibility to azoxymethane-induced aberrant crypt foci, preneoplastic lesions in the colon. Furthermore, transgenic PKC βII mice exhibit elevated colonic β-catenin levels and decreased glycogen synthase kinase 3β activity, indicating that PKC βII stimulates the Wnt/adenomatous polyposis coli (APC)/β-catenin proliferative signaling pathway in vivo. These data demonstrate a direct role for PKC βII in colonic epithelial cell proliferation and colon carcinogenesis, possibly through activation of the APC/β-catenin signaling pathway.

scholarly journals Protein Kinase C Signaling Mediates a Program of Cell Cycle Withdrawal in the Intestinal Epithelium

2000 ◽  
Vol 151 (4) ◽  
pp. 763-778 ◽  
Author(s):  
Mark R. Frey ◽  
Jennifer A. Clark ◽  
Olga Leontieva ◽  
Joshua M. Uronis ◽  
Adrian R. Black ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Intestinal Epithelium ◽  
Molecular Mechanisms ◽  
Model Systems ◽  
Intestinal Epithelial ◽  
Kinase C

Members of the protein kinase C (PKC) family of signal transduction molecules have been widely implicated in regulation of cell growth and differentiation, although the underlying molecular mechanisms involved remain poorly defined. Using combined in vitro and in vivo intestinal epithelial model systems, we demonstrate that PKC signaling can trigger a coordinated program of molecular events leading to cell cycle withdrawal into G0. PKC activation in the IEC-18 intestinal crypt cell line resulted in rapid downregulation of D-type cyclins and differential induction of p21waf1/cip1 and p27kip1, thus targeting all of the major G1/S cyclin-dependent kinase complexes. These events were associated with coordinated alterations in expression and phosphorylation of the pocket proteins p107, pRb, and p130 that drive cells to exit the cell cycle into G0 as indicated by concomitant downregulation of the DNA licensing factor cdc6. Manipulation of PKC isozyme levels in IEC-18 cells demonstrated that PKCα alone can trigger hallmark events of cell cycle withdrawal in intestinal epithelial cells. Notably, analysis of the developmental control of cell cycle regulatory molecules along the crypt–villus axis revealed that PKCα activation is appropriately positioned within intestinal crypts to trigger this program of cell cycle exit–specific events in situ. Together, these data point to PKCα as a key regulator of cell cycle withdrawal in the intestinal epithelium.

scholarly journals Protein kinase C βII and TGFβRII in ω-3 fatty acid–mediated inhibition of colon carcinogenesis

2002 ◽  
Vol 157 (6) ◽  
pp. 915-920 ◽  
Author(s):  
Nicole R. Murray ◽  
Capella Weems ◽  
Lu Chen ◽  
Jessica Leon ◽  
Wangsheng Yu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Colon Carcinogenesis ◽  
Transforming Growth Factor Β ◽  
Kinase C ◽  
Elevated Expression ◽  
Β Receptor

Încreasing evidence demonstrates that protein kinase C βII (PKCβII) promotes colon carcinogenesis. We previously reported that colonic PKCβII is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCβII in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCβII represses transforming growth factor β receptor type II (TGFβRII) expression and reduces sensitivity to TGF-β–mediated growth inhibition in intestinal epithelial cells. Transgenic PKCβII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFβRII expression. Chemopreventive dietary ω-3 fatty acids inhibit colonic PKCβII activity in vivo and block PKCβII-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFβRII expression in the colonic epithelium of transgenic PKCβII mice. These data indicate that dietary ω-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCβII signaling and restoration of TGF-β responsiveness.

scholarly journals Deletion of Protein Kinase C-ε Signaling Pathway Induces Glomerulosclerosis and Tubulointerstitial Fibrosis In Vivo

2007 ◽  
Vol 18 (4) ◽  
pp. 1190-1198 ◽  
Author(s):  
Matthias Meier ◽  
Jan Menne ◽  
Joon-Keun Park ◽  
Marcel Holtz ◽  
Faikah Gueler ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Tubulointerstitial Fibrosis ◽  
Kinase C

scholarly journals Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1470-1479 ◽  
Author(s):  
Arturo E. Gonzalez-Iglesias ◽  
Takayo Murano ◽  
Shuo Li ◽  
Melanija Tomić ◽  
Stanko S. Stojilkovic
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Pertussis Toxin ◽  
Glycogen Synthase ◽  
Inward Rectifier ◽  
Glycogen Synthase Kinase 3 ◽  
K Channels ◽  
Voltage Gated ◽  
Kinase C

Dopamine D2 receptors signal through the pertussis toxin (PTX)-sensitive Gi/o and PTX-insensitive Gz proteins, as well as through a G protein-independent, β-arrestin/glycogen synthase kinase-3-dependent pathway. Activation of these receptors in pituitary lactotrophs leads to inhibition of prolactin (PRL) release. It has been suggested that this inhibition occurs through the Gi/o-α protein-mediated inhibition of cAMP production and/or Gi/o-βγ dimer-mediated activation of inward rectifier K+ channels and inhibition of voltage-gated Ca2+ channels. Here we show that the dopamine agonist-induced inhibition of spontaneous Ca2+ influx and release of prestored PRL was preserved when cAMP levels were elevated by forskolin treatment. We further observed that dopamine agonists inhibited both spontaneous and depolarization-induced Ca2+ influx in untreated but not in PTX-treated cells. This inhibition was also observed in cells with blocked inward rectifier K+ channels, suggesting that the dopamine effect on voltage-gated Ca2+ channel gating is sufficient to inhibit spontaneous Ca2+ influx. However, agonist-induced inhibition of PRL release was only partially relieved in PTX-treated cells, indicating that dopamine receptors also inhibit exocytosis downstream of voltage-gated Ca2+ influx. The PTX-insensitive step in agonist-induced inhibition of PRL release was not affected by the addition of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and lithium, an inhibitor of glycogen synthase kinase-3, but was attenuated in the presence of phorbol 12-myristate 13-acetate, which inhibits Gz signaling pathway in a protein kinase C-dependent manner. Thus, dopamine inhibits basal PRL release by blocking voltage-gated Ca2+ influx through the PTX-sensitive signaling pathway and by desensitizing Ca2+ secretion coupling through the PTX-insensitive and protein kinase C-sensitive signaling pathway.

In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha

2000 ◽  
Vol 33 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Shwu-Bin Lin ◽  
Li-Ching Wu ◽  
Siao-Ling Huang ◽  
Hui-Lun Hsu ◽  
Sung-Hwa Hsieh ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tumor Cells ◽  
Rat Liver ◽  
Antisense Oligonucleotide ◽  
Epithelial Tumor ◽  
Kinase C ◽  
Epithelial Tumor Cells

Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

1990 ◽  
Vol 122 (3) ◽  
pp. 403-408
Author(s):  
Ph. Touraine ◽  
P. Birman ◽  
F. Bai-Grenier ◽  
C. Dubray ◽  
F. Peillon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Plasma Prolactin ◽  
Estradiol Treatment ◽  
Kinase C ◽  
Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

A Study of Protein Kinase C Isozyme Distribution in Relation to Bcl-2 Expression during Apoptosis of Epithelial Cells in Vivo

1993 ◽  
Vol 207 (1) ◽  
pp. 68-73 ◽  
Author(s):  
Kirstine A. Knox ◽  
Gerald D. Johnson ◽  
John Gordon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Kinase C
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