Abstract
The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 μM dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.
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References
Zemecnik PC, Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligonucleotide. Proc Natl Acad Sci USA 75:280–284
Helene C, Toulme JJ (1990) Specific regulation of gene expression by antisense, sense and antigene nucleic acids. biochim Biophys Acta 1049:99–125
Calabretta B (1991) Inhibition of protooncogene expression by antisense oligonucleotides: biological and therapeutic implications. Cancer Res 51:4505–4510
Bravo R, Frank R, Blundel PA, Bravo HM (1987) Cyclin/PCNA is the auxillary protein of DNA polymerase-delta. Nature 326:515–517
Jolio EC, Celis A (1985) Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase. Proc Natl Acad Sci USA 82:3262–3266
Yonemura Y, Kimura H, Fushida S, Tugawa K, Nakai Y, Kaji M, Funseca L, Yamaguchi A, Miyazaki I (1993) Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy. Cancer 71:2448–2453
Jaskulski D, DeRiel JK, Mercer WE, Calabretta B, Baserga R (1988) Inhibition of cellular proliferation by antisense oligonucleotides of PCNA cyclin. Science 240:1544–1546
Speir BS, Stephen EE (1992) Inhibition of smooth muscle cell proliferation by antisense oligonucleotides targeting the messenger RNA encoding proliferating cell nuclear antigen. Circulation 86:538–547
Agrawal S, Temsamani J, Tang JY (1991) Pharmacokinetics, biodistribution, and stability of oligonucleotide phosphorotioate in mice. Proc Natl Acad Sci USA 88:7595–7599
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Sakakura, C., Hagiwara, A., Tsujimoto, H. et al. The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines. Surg Today 25, 184–186 (1995). https://doi.org/10.1007/BF00311097
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DOI: https://doi.org/10.1007/BF00311097