The potential clinical value of GML and the p53 gene as a predictor of chemosensitivity for colorectal cancer

被引：6

作者：

Hashimoto Y. ^{[1
]}

Ueda K. ^{[1
]}

Minami K. ^{[1
]}

Watatani M. ^{[1
]}

机构：

[1] First Department of Surgery, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511

来源：

International Journal of Clinical Oncology | 2001年 / 6卷 / 2期

关键词：

5-FU; Chemosensitivity; Colorectal cancer; GML; MMC; P53;

D O I：

10.1007/PL00012089

中图分类号：

学科分类号：

摘要：

Background. Adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC) has commonly been used after resection of colorectal cancer. The aim of this study was to determine the predictive value of p53 mutation or the expression of GML, a target of p53, for sensitivity to 5-FU and MMC. Methods. We analyzed p53 mutations and the expression of GML in six colorectal cancer cell lines (SW837, DLD-1, RPMI4788, WiDr, HT-29, and HCT116), and examined the correlation between genetic changes and in-vitro chemosensitivity to MMC and 5-FU by measuring the colony-forming ability in these cell lines. We also introduced GML cDNA into a cell line that lacked endogenous GML expression to investigate changes in sensitivity to MMC and 5-FU. Results. The sensitivity to MMC was highest in HCT116, which had no p53 gene abnormalities and expressed endogenous GML, and lowest in RPMI4788 cells, which had neither p53 gene abnormalities nor expression of endogenous GML. For 5-FU treatment with 24-h exposure, HCT116 showed the highest sensitivity, and SW837, which had p53 mutations without expression of GML, showed the lowest sensitivity. The introduction of GML cDNA to RPMI4788 (RPMI4788-GML) showed that the sensitivity of RPMI4788-GML to MMC was enhanced almost to the level of HCT116 cells. However, when RPMI4788-GML were exposed to 5-FU for 24-h, the sensitivity of RPMI4788-GML was slightly increased compared with that of the parental cells, but was slightly lower than that of HCT116. Conclusion. GML expression and p53 mutation in colorectal cancer may be useful predictive genetic markers for sensitivity to MMC and 5-FU, respectively.

引用

页码：90 / 96

页数：6

共 40 条

[1]

DSchilsky R.L., Kelsen D., Moore T.D., Et al., Systemic therapy for recurrent or metastatic disease, pp. 893-978, (1995)

[2]

Kodaira S., The current status of postoperative adjuvant chemotherapy for colorectal cancer, Jpn J Cancer Chemother, 24, pp. 1230-1238, (1997)

[3]

Kerr John F.R., Winterford C.M., Harmon B.V., Et al., Apoptosis: Its significance in cancer and cancer therapy, Cancer, 73, pp. 2013-2026, (1994)

[4]

Hickman J.A., Potten C.S., Merritt A.J., Et al., Apoptosis and cancer chemotherapy, Phil Trans R Soc Lond B, 345, pp. 319-325, (1994)

[5]

Zheng M., Zhang H.W.H., Shen Q.O.B., Et al., The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells, J Cancer Res Clin Oncol, 125, pp. 357-360, (1999)

[6]

Mueller H., Eppenberger U., The dual role of mutant p53 protein in chemosensitivity of human cancers, Anticancer Res, 16, pp. 3845-3848, (1996)

[7]

Suzuki K., Kazui T., Yoshida M., Et al., Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro, Jpn J Clin Oncol, 29, pp. 323-331, (1999)

[8]

Nita M., Nagawa H., Tominaga O., Et al., 5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins, Br J Cancer, 78, pp. 986-992, (1998)

[9]

Yoneda K., Yamamoto T., Osaki T., p53- and p21- independent apoptosis of squamous cell carcinoma cells induced by 5-fluorouracil and radiation, Oral Oncol, 34, pp. 529-537, (1998)

[10]

Yang B., Eshleman J.R., Berger N.A., Et al., Wild-type p53 protein potentiates cytotoxicity of therapeutic agents in human colon cancer cells, Clin Cancer Res, 2, pp. 1649-1657, (1996)

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