title: Glutathione and glutathione peroxidase expression in breast cancer: an immunohistochemical and molecular study.
abstract: The use of prognostic markers for breast cancer allows therapeutic strategies to be defined more efficiently. The expression of glutathione (GSH) and glutathione peroxidase (GPX) in tumor cells has been evaluated as a predictor of prognosis and response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results showed that high GSH expression was associated with tumors negative for the estrogen receptor (ER) (P<0.05), and GPX expression was associated with tumors negative for the progesterone receptor (PR) and patient mortality. Focusing on the 37 patients who received adjuvant chemotherapy/radiotherapy (Group I), high expression of GPX was associated with a high rate of patient mortality (P<0.05). The 19 patients who received only adjuvant chemotherapy (Group II) showed high expression of GSH in relation to metastasis (P<0.05). In addition, high levels of GPX expression were significantly associated with a shorter overall survival (P<0.05). To confirm this, the expression of precursor genes of GSH [glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS)] and the GPX gene was analyzed using quantitative PCR in cultured neoplastic mammary cells treated with doxorubicin. Doxorubicin treatment was able to eliminate tumor cells without alterations in the gene expression of GSS, but led to underexpression of the GCLC and GPX genes. Our results suggest that high levels of GPX may be related to the development of resistance to chemotherapy in these tumors, response to treatment and the clinical course of the breast cancer patients.
authors.affiliation: Department of Biology, Sao Paulo State University - UNESP/IBILCE, 15090-000 São José do Rio Preto, SP, Brazil.
authors.forename: Bruna Victorasso
authors.initials: BV
authors.lastname: Jardim
authors.forename: Marina Gobbe
authors.initials: MG
authors.lastname: Moschetta
authors.forename: Camila
authors.initials: C
authors.lastname: Leonel
authors.forename: Gabriela Bottaro
authors.initials: GB
authors.lastname: Gelaleti
authors.forename: Vitor Rafael
authors.initials: VR
authors.lastname: Regiani
authors.forename: Lívia Carvalho
authors.initials: LC
authors.lastname: Ferreira
authors.forename: Juliana Ramos
authors.initials: JR
authors.lastname: Lopes
authors.forename: Debora Ap Pires de Campos
authors.initials: DA
authors.lastname: Zuccari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D005978:Glutathione; D005979:Glutathione Peroxidase; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human