Glutathion s transferase π indicates chemotherapy resistance in breast cancer

Fengxi Su, Xiaoqu Hu, Weijuan Jia, Chang Gong, Erwei Song, P. Hamar

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background. Breast cancer is the most common malignant disease of women. Pathologic response of breast cancer to chemotherapy has a great prognostic importance. Glutathion S Transferases (GSTs) might detoxify chemotherapeutic drugs within the cancer cells, thus contributing to chemotherapy resistance. The pi isoenzyme of GSTs seems to be of great relevance. Thus, we hypothesized that GSTpi expression in cancer biopsy can be a prognostic indicator for resistance to chemotherapy. To test this hypothesis, we evaluated before and after chemotherapy, tumor size, apoptosis of tumor cells with TUNEL assay, and proliferation of tumor cells by determining PCNA expression in biopsy samples, or in the surgically removed tumor tissue of GSTpi (-), and GSTpi (+) cases. Materials and methods. GSTpi immunoreactivity was determined in 42 female patients with breast cancer. Patients were divided into two groups according to the expression of GSTpi in the pre-treatment biopsy specimen: (+) (n = 22) and (n = 20) samples were analyzed. Surgery was performed 2 weeks after a single intravenous injection of the chemotherapeutic drugs [5-fluorouracil, adriamycin, mitomycin (FAM protocol)]. Results. Pre-chemotherapy values of tumor size, apoptosis, or proliferation did not differ between GSTpi (-) and (+) samples. Chemotherapy significantly inhibited tumor growth, and cell proliferation, and induced apoptosis in GSTpi (-) cases. However, these effects were significantly reduced in GSTpi (+) patients. Conclusion. These results suggest, that the presence of GSTpi in breast cancer tissue is a bad prognostic indicator, and these tumors are largely resistant to chemotherapy. Thus, GSTpi might be important in inactivating one or more of the chemotherapeutic agents used in this treatment.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalJournal of Surgical Research
Volume113
Issue number1
DOIs
Publication statusPublished - Jul 2003

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Glutathione Transferase
Breast Neoplasms
Drug Therapy
Neoplasms
Apoptosis
Biopsy
Cell Proliferation
Glutathione S-Transferase pi
In Situ Nick-End Labeling
Proliferating Cell Nuclear Antigen
Mitomycin
Intravenous Injections
Fluorouracil
Pharmaceutical Preparations
Doxorubicin
Isoenzymes
Therapeutics
Growth

Keywords

  • Apoptosis
  • Breast cancer
  • Chemotherapy resistance
  • FAM
  • GSTpi
  • MDR

ASJC Scopus subject areas

  • Surgery

Cite this

Glutathion s transferase π indicates chemotherapy resistance in breast cancer. / Su, Fengxi; Hu, Xiaoqu; Jia, Weijuan; Gong, Chang; Song, Erwei; Hamar, P.

In: Journal of Surgical Research, Vol. 113, No. 1, 07.2003, p. 102-108.

Research output: Contribution to journalArticle

Su, Fengxi ; Hu, Xiaoqu ; Jia, Weijuan ; Gong, Chang ; Song, Erwei ; Hamar, P. / Glutathion s transferase π indicates chemotherapy resistance in breast cancer. In: Journal of Surgical Research. 2003 ; Vol. 113, No. 1. pp. 102-108.
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AB - Background. Breast cancer is the most common malignant disease of women. Pathologic response of breast cancer to chemotherapy has a great prognostic importance. Glutathion S Transferases (GSTs) might detoxify chemotherapeutic drugs within the cancer cells, thus contributing to chemotherapy resistance. The pi isoenzyme of GSTs seems to be of great relevance. Thus, we hypothesized that GSTpi expression in cancer biopsy can be a prognostic indicator for resistance to chemotherapy. To test this hypothesis, we evaluated before and after chemotherapy, tumor size, apoptosis of tumor cells with TUNEL assay, and proliferation of tumor cells by determining PCNA expression in biopsy samples, or in the surgically removed tumor tissue of GSTpi (-), and GSTpi (+) cases. Materials and methods. GSTpi immunoreactivity was determined in 42 female patients with breast cancer. Patients were divided into two groups according to the expression of GSTpi in the pre-treatment biopsy specimen: (+) (n = 22) and (n = 20) samples were analyzed. Surgery was performed 2 weeks after a single intravenous injection of the chemotherapeutic drugs [5-fluorouracil, adriamycin, mitomycin (FAM protocol)]. Results. Pre-chemotherapy values of tumor size, apoptosis, or proliferation did not differ between GSTpi (-) and (+) samples. Chemotherapy significantly inhibited tumor growth, and cell proliferation, and induced apoptosis in GSTpi (-) cases. However, these effects were significantly reduced in GSTpi (+) patients. Conclusion. These results suggest, that the presence of GSTpi in breast cancer tissue is a bad prognostic indicator, and these tumors are largely resistant to chemotherapy. Thus, GSTpi might be important in inactivating one or more of the chemotherapeutic agents used in this treatment.

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