THE ANTIPROLIFERATIVE EFFECT OF PROLIFERATING CELL NUCLEAR ANTIGEN-SPECIFIC ANTISENSE OLIGONUCLEOTIDES ON HUMAN GASTRIC-CANCER CELL-LINES

被引：26

作者：

SAKAMURA, C

HAGIWARA, A

TSUJIMOTO, H

OZAKI, K

SAKAKIBARA, T

OYAMA, T

OGAKI, M

TAKAHASHI, T

机构：

[1] First Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602, Kamigyo-ku, Kawaramachi-dori

来源：

SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY | 1995年 / 25卷 / 02期

关键词：

PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA); GASTRIC CANCER; ANTISENSE OLIGONUCLEOTIDES; GENE THERAPY;

D O I：

10.1007/BF00311097

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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 mu M 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.

引用

页码：184 / 186

页数：3

共 9 条

[1]

Zemecnik P.C., Stephenson M.L., Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligonucleotide, Proceedings of the National Academy of Sciences, 75, pp. 280-284, (1978)

[2]

Helene C., Toulme J.J., Specific regulation of gene expression by antisense, sense and antigene nucleic acids, biochim Biophys Acta, 1049, pp. 99-125, (1990)

[3]

Calabretta B., Inhibition of protooncogene expression by antisense oligonucleotides: biological and therapeutic implications, Cancer Res, 51, pp. 4505-4510, (1991)

[4]

Bravo R., Frank R., Blundel P.A., Bravo H.M., Cyclin/PCNA is the auxillary protein of DNA polymerase-delta, Nature, 326, pp. 515-517, (1987)

[5]

Jolio E.C., Celis A., 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, pp. 3262-3266, (1985)

[6]

Yonemura Y., Kimura H., Fushida S., Tugawa K., Nakai Y., Kaji M., Funseca L., Yamaguchi A., Miyazaki I., Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy, Cancer, 71, pp. 2448-2453, (1993)

[7]

Jaskulski D., DeRiel J.K., Mercer W.E., Calabretta B., Baserga R., Inhibition of cellular proliferation by antisense oligonucleotides of PCNA cyclin, Science, 240, pp. 1544-1546, (1988)

[8]

Speir B.S., Stephen E.E., Inhibition of smooth muscle cell proliferation by antisense oligonucleotides targeting the messenger RNA encoding proliferating cell nuclear antigen, Circulation, 86, pp. 538-547, (1992)

[9]

Agrawal S., Teamani J., Tang J.Y., Pharmacokinetics, biodistribution, and stability of oligonucleotide phosphorotioate in mice, Proc Natl Acad Sci USA, 88, pp. 7595-7599, (1991)

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