Absence of beta-tubulin gene mutation in gastric carcinoma

被引：2

作者：

Naomi Urano

Yoshiyuki Fujiwara

Seiichi Hasegawa

Yasuo Miyoshi

Shinzaburo Noguchi

Shuji Takiguchi

Takushi Yasuda

Masahiko Yano

Morito Monden

机构：

[1] Dept. of Surg. and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, 2-2

[2] Department of Surgical Oncology, Graduate School of Medicine, Osaka University, Osaka

来源：

Gastric Cancer | 2003年 / 6卷 / 2期

关键词：

Beta-tubulin gene; Drug resistance; Gastric cancer; Gene mutation; SSCP;

D O I：

10.1007/s10120-003-0235-6

中图分类号：

学科分类号：

摘要：

Background. Effective chemotherapy for advanced gastric cancer is yet to be established. Taxanes, novel anticancer drugs which bind to beta-tubulin and prevent disruption of microtubules, are newly approved and promising agents for advanced and recurrent gastric cancer. To predict the chemoresistance to a taxan in gastric cancer, we examined the genetic mutations of the beta-tubulin gene. Methods. Fifty pairs of gastric tumor and normal mucosa tissues were obtained from operations and the genomic DNA was extracted from each specimen. The four exons of the beta-tubulin gene were amplified for DNA mutations by single-strand conformation polymorphism (SSCP) methods and sequencing analysis. Results. Nine (18%) of 50 patients with gastric cancer had two kinds of silent variations of the beta-tubulin gene in exon 4. Three kinds of intronic variations were detected in exons 1, 2, and 3. However, no genetic alterations that would change the beta-tubulin protein structure were detected in any of the 50 gastric tumors. Conclusion. Our findings indicate that mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer.

引用

页码：108 / 112

页数：4

共 19 条

[1] Yamaguchi K., Tada M., Horikoshi N., Otani T., Takiuchi H., Saitoh S.T., Et al., Phase study of paclitaxel with 3-h infusion in patients with advanced gastric cancer, Gastric Cancer, 5, pp. 90-95, (2002)
[2] Ohtsu A., Boku N., Tamura F., Muro K., Shimada Y., Saigenji K., Et al., An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer, Am J Clin Oncol, 21, pp. 416-419, (1998)
[3] Parness J., Horwitz S.B., Taxol binds to polymerized tubulin in vitro, J Cell Biol, 91, pp. 479-487, (1981)
[4] Horwitz S.B., Cohen D., Rao S., Taxol: Mechanism of action and resistance, Monogr J Natl Cancer Inst, 5, pp. 55-61, (1993)
[5] Milross C.G., Mason K.A., Hunter N.R., Chung Y.K., Peters L.J., Milas L., Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel, J Natl Cancer Inst, 88, pp. 1308-1314, (1996)
[6] Long B.H., Fairchild C.R., Paclitaxel inhibits progression of mitotic cell to G phase by interference with spindle formation without affecting other microtubule functions during anaphase and telophase, Cancer Res, 54, pp. 4355-4361, (1994)
[7] Diaz J.F., Andreu M.J., Assembly of purified GDP-tubulin into microtubule induced by taxol and taxotere: Reversibility, ligand and stoichiometry, and competition, Biochemistry, 32, pp. 2747-2755, (1993)
[8] Rao S., Krauss N.E., Heeding J.M., Swindell C.S., Ringel I., George A.O., Et al., 3′-(p-azidobenzamido) taxol photolabels the N-terminal 31 amino acids of beta-tubulin, J Biol Chem, 269, pp. 3132-3134, (1994)
[9] Schibler M.T., Cabral F., Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha- and beta-tubulin, J Cell Biol, 102, pp. 1522-1531, (1986)
[10] Ohta S.K., Nishio N., Kubota T., Ohmori T., Funayama Y., Ohira T., Et al., Characterization of a taxol-resistant human small-cell lung cancer cell line, Jpn J Cancer Res, 85, pp. 290-297, (1994)

← 1 2 →