In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 64, No. 16 ( 2004-08-15), p. 5787-5794
Abstract:
Protein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCα, PKCβ1, and PKCβ2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCα-AS and PKCβ1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCα-AS and PKCβ1-AS transfectants. PKCα-AS and PKCβ1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCβ2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCα and PKCβ1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCα or PKCβ1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCα or PKCβ1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCα and PKCβ1 by antisense method is a promising therapy for gastric cancer.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-03-1172
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2004
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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