scholarly journals Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression.

1990 ◽  
Vol 10 (9) ◽  
pp. 4650-4657 ◽  
Author(s):  
P M Choi ◽  
K M Tchou-Wong ◽  
I B Weinstein
Keyword(s):  
Colon Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Line ◽  
Cell Lines ◽  
Control Cell ◽  
Tumor Promoter ◽  
Vector System ◽  
Human Colon Cancer ◽  
Kinase C

By using a retrovirus-derived vector system, we generated derivatives of the human colon cancer cell line HT29 that stably overexpress a full-length cDNA encoding the beta 1 isoform of rat protein kinase C (PKC). Two of these cell lines, PKC6 and PKC7, displayed an 11- to 15-fold increase in PKC activity when compared with the C1 control cell line that carries the vector lacking the PKC cDNA insert. Both of the overexpresser cell lines exhibited striking alterations in morphology when exposed to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Following exposure to TPA, PKC6 and PKC7 cells displayed increased doubling time, decreased saturation density, and loss of anchorage-independent growth in soft agar; but these effects were not seen with the C1 cells. Also, in contrast to the control cells, the PKC-overproducing cells failed to display evidence of differentiation, as measured by alkaline phosphatase activity, when exposed to sodium butyrate. In addition, the PKC-overexpresser cells displayed decreased tumorigenicity in nude mice, even in the absence of treatment with TPA. These results provide the first direct evidence that PKC can inhibit tumor cell growth. Thus, in some tumors, PKC might act as a growth-suppressor gene.

Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression

1990 ◽  
Vol 10 (9) ◽  
pp. 4650-4657
Author(s):  
P M Choi ◽  
K M Tchou-Wong ◽  
I B Weinstein
Keyword(s):  
Colon Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Line ◽  
Cell Lines ◽  
Control Cell ◽  
Tumor Promoter ◽  
Vector System ◽  
Human Colon Cancer ◽  
Kinase C

By using a retrovirus-derived vector system, we generated derivatives of the human colon cancer cell line HT29 that stably overexpress a full-length cDNA encoding the beta 1 isoform of rat protein kinase C (PKC). Two of these cell lines, PKC6 and PKC7, displayed an 11- to 15-fold increase in PKC activity when compared with the C1 control cell line that carries the vector lacking the PKC cDNA insert. Both of the overexpresser cell lines exhibited striking alterations in morphology when exposed to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Following exposure to TPA, PKC6 and PKC7 cells displayed increased doubling time, decreased saturation density, and loss of anchorage-independent growth in soft agar; but these effects were not seen with the C1 cells. Also, in contrast to the control cells, the PKC-overproducing cells failed to display evidence of differentiation, as measured by alkaline phosphatase activity, when exposed to sodium butyrate. In addition, the PKC-overexpresser cells displayed decreased tumorigenicity in nude mice, even in the absence of treatment with TPA. These results provide the first direct evidence that PKC can inhibit tumor cell growth. Thus, in some tumors, PKC might act as a growth-suppressor gene.

Distinct protein kinase C isozymes signal mitogenesis and apoptosis in human colon cancer cells

1999 ◽  
Vol 117 (4) ◽  
pp. 848-857 ◽  
Author(s):  
Shaun G. Weller ◽  
Irene K. Klein ◽  
Robert C. Penington ◽  
William E. Karnes
Keyword(s):  
Colon Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Kinase C ◽  
Human Colon Cancer Cells

Enzastaurin (LY317615), an Oral Protein Kinase C β Inhibitor, Induces Apoptosis in Multiple Myeloma Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1577-1577
Author(s):  
Mujahid A. Rizvi ◽  
Kulsoom Ghias ◽  
Katharine M. Davies ◽  
Chunguang Ma ◽  
Nancy L. Krett ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Myeloma Cell ◽  
Akt Pathway ◽  
Kinase C

Abstract The protein kinase C (PKC) family consists of 11 serine/threonine protein kinase isoforms that are involved with cell proliferation and differentiation, gene transcription, and tumor-induced angiogenesis. The PKC pathway has been shown to play a role in the regulation of cell growth in several hematologic malignancies. However, in multiple myeloma (MM), the role of the PKC pathway has not been extensively studied. Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of the PKC β isozyme. Enzastaurin has been reported to induce apoptosis and suppress proliferation in the HCT116 colon cancer cell line by inhibiting the AKT pathway. The objective of this study was to assess the efficacy of Enzastaurin in inducing apoptosis in MM cell lines and to investigate possible mechanisms of apoptosis. A spectrum of MM cell lines, with unique characteristics (dexamethasone-sensitive, dexamethasone-resistant, chemotherapy-sensitive, chemotherapy-resistant) were treated with Enzastaurin. There is evidence of cell death in all cell lines at clinically significant concentrations (1–3μM) after 72 hours of treatment. The dexamethasone-sensitive MM1.S cell line was used to further assess the effect of Enzastaurin in the presence of dexamethasone, insulin-like growth factor-1 (IGF-1), and IL-6. IGF-1 and IL-6 are potent growth factors for MM and have been observed to blunt the cytotoxic activity of dexamethasone. Dexamethasone and Enzastaurin appear to have an additive effect in the induction of apoptosis. In addition, while IGF-1 slightly decreases the effect of Enzastaurin, IL-6 has no effect. Enzastaurin treatment also induces a decrease in GSK3β and AKTSerine473 phosphorylation. GSK3β phosphorylation is thought to be a reliable pharmacodynamic marker for Enzastaurin activity. In conclusion, these data indicate that Enzastaurin induces apoptosis in MM cells and suppression of the AKT pathway may be one of the mechanisms by which Enzastaurin exerts its anti-myeloma activity.

Selective low level of protein kinase C isozyme in a tumor promoter-dependent mouse leukemia cell line

1989 ◽  
Vol 164 (3) ◽  
pp. 1397-1401 ◽  
Author(s):  
Toshio Tanaka ◽  
Masatoshi Hagiwara ◽  
Hiroyoshi Hidaka ◽  
Kazuo Nunoki ◽  
Hisataka Ohta ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Line ◽  
Leukemia Cell ◽  
Tumor Promoter ◽  
Leukemia Cell Line ◽  
Mouse Leukemia ◽  
Low Level ◽  
Kinase C

Cells that overproduce protein kinase C are more susceptible to transformation by an activated H-ras oncogene

1989 ◽  
Vol 9 (6) ◽  
pp. 2641-2647
Author(s):  
W L Hsiao ◽  
G M Housey ◽  
M D Johnson ◽  
I B Weinstein
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cell Transformation ◽  
Synergistic Effects ◽  
Control Cell ◽  
Fold Increase ◽  
Fibroblast Cell ◽  
Ras Oncogene ◽  
Kinase C

We recently developed rat fibroblast cell lines that stably overproduce high levels of the beta 1 form of protein kinase C (PKC). These cells display several disorders in growth control and form small microscopic colonies in agar. In the present study we demonstrate that one of these cell lines, R6-PKC3, is extremely susceptible to transformation by an activated human bladder cancer c-H-ras oncogene (T24). Compared with control cell line R6-C1, T24-transfected R6-PKC3 cells yielded a 10-fold increase in the formation of large colonies in agar. Cell lines established from these colonies displayed a highly transformed morphology, expressed the T24-encoded p21 ras protein, continued to express high levels of PKC, and were highly tumorigenic in nude mice. These results provide genetic evidence that PKC mediates some of the effects of the c-H-ras oncogene on cell transformation. Data are also presented suggesting that optimum synergistic effects between c-H-ras and PKC require critical levels of their respective activities. These findings may be relevant to the process of multistage carcinogenesis in tissues containing cells with an activated c-H-ras oncogene.

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