ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Er, T.-K.
Right arrow Articles by Tsai, L.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Er, T.-K.
Right arrow Articles by Tsai, L.-Y.
Annals of Clinical & Laboratory Science 34:159-164 (2004)
© 2004 Association of Clinical Scientists

Differential Expression of Manganese Containing Superoxide Dismutase in Patients with Breast Cancer in Taiwan

Tze-Kiong Er1, Ming-Feng Hou2, Eing-Mei Tsa3, Jau-Nan Lee3 and Li-Yu Tsai4
1 Graduate Institute of Medicine, 2 Departments of Surgery, 3 Obstetrics/Gynecology, and 4 Clinical Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

Address correspondence to Li-Yu Tsai PhD, Department of Clinical Chemistry, School of Technology for Medical Science, Kaohsiung Medical University, 100 Shi-Chuan 1st Road, San Ming District, Kaohsiung, Taiwan, ROC; tel 886 7 312 1101, ext 7262, 7263; fax 886 7 237 0544; e-mail tsliyu{at}kmu.edu.tw.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
This study used Western blot analysis to measure the expression of superoxide dismutases (Mn-SOD and Cu/Zn-SOD) in breast cancer tissues from 57 patients. Mn-SOD expression in the breast cancer tissues averaged 1.5-fold higher than in the adjacent tumor-free tissues (p <0.05). There was no significant difference in Cu/Zn-SOD expression between neoplastic and tumor-free breast tissues. This study shows a significant increase of Mn-SOD expression in breast cancer tissues. The authors speculate that up-regulation of Mn-SOD expression induced by oxidative stress or local inflammation may contribute a selective growth advantage to tumor cells compared to their normal counterparts.

(received 2 July 2003; accepted 24 January 2004)

Keywords: breast cancer, Mn-SOD, Cu/Zn-SOD, reactive oxygen species


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Carcinoma of the breast, which is the third most common cancer worldwide, accounts for the highest morbidity and mortality [1]. Annually 910,000 new patients are diagnosed with breast cancer and 376,000 women die of this disease [2]. Breast cancer has become the second leading cancer of women in Taiwan. Its incidence has increased in Taiwan and other areas of Asia over the past decade. In Taiwan, the incidence of female breast cancer increased from 26.8 to 35.7 cases/million women from 1988 to 2002. The standardized death rate of females with breast cancer increased by 9.1% in 1999 [3]. The data indicate that this rise was more pronounced in young women compared to an older group. The age-specific incidence rates peaked between the ages of 45 and 59 yr [3,4].

The etiology of breast cancer is multifactorial. Hormonal, genetic, and environmental factors interplay in the pathogenesis of breast cancer [5]. Increased lifetime exposure to endogenous or exogenous hormones is a major risk factor in the development of breast cancer [6]. Several genes (eg, BRCA1, BRCA2, HER-2/neu, p53) are linked to breast cancer susceptibility and development [7,8].

Reactive oxygen species (ROS) are by-products generated endogenously by all aerobic cells as a result of oxygen metabolism. At high concentrations, ROS, which are highly reactive, exert harmful effects on living organisms, inducing oxidative damage to their DNA and cell membranes. The accumulation of DNA damage is believed to contribute to carcinogenesis [9].

Cells have efficient protection against harmful effects of ROS by enzymatic and non-enzymatic antioxidant mechanisms. Superoxide dismutase (SOD), one of the main antioxidant enzymes, catalyzes the dismutation of highly reactive O2–• to O2 and H2O2, a less reactive ROS. H2O2 and other peroxides in the cell are then consumed by multiple enzymes, such as catalase and glutathione peroxide [10]. There are two major forms of SOD in human cells: Mn-containing SOD (Mn-SOD), which is primarily localized in mitochondria, and Cu/Zn-containing SOD (Cu/Zn-SOD), which is primarily localized in the cytosol [11]. Mn-SOD is one of the most important antioxidant enzymes against both endogenous and exogenous superoxides [12]. Basal expression of Mn-SOD in cells is usually low and often barely detectable, but the enzyme is induced by hyperoxia [13], irradiation [14], cytokines [15], and changes in cellular redox state [16].

Previous investigators have measured the enzymatic activities of the SODs in breast cancers [17,18], but protein expression of the SODs in breast cancers has not been as thoroughly studied. The present study employs Western blot analysis to assess the protein expression of Mn-SOD and Cu/Zn-SOD in tissues of women with breast carcinoma.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patients and tissue specimens.  Fifty-seven newly diagnosed breast cancer patients (age 49.9±10.3 yr) from Kaohsiung Medical University Hospital, who had not undergone any treatment for their tumors, were chosen randomly for the study. The patients were clinically classified as stage I (7 patients), stage II (45 patients), and stage III (5 patients). Table 1Go shows the general characteristics of the patients.


View this table:
[in this window]
[in a new window]
  		Table 1. Demographic and clinical characteristics of the breast cancer patients
 
Paired samples (n = 114) of fresh breast tumor and adjacent tumor-free tissue were obtained from the cancer patients at surgery and immediately placed in cold 0.9% NaCl solution, perfused with the same solution to remove blood cells, blotted on filter paper, and weighed. The tissues were stored in liquid nitrogen until the subsequent processing.

Protein extraction.  Breast specimens (tumor or tumor-free) were weighed and homogenized under standardized conditions. Total protein was extracted from the tissue homogenate in lysate buffer (40 mM HEPES, 1.25 µg/ml leupeptin, 2.5 µg/ml aprotinin, 1.25 µg/ml pepstatin, 0.125 mg/ml pefabloc, 0.09 mM DTT, and 1% NP40) and centrifuged at 10,000 x g for 15 min at 4°C. While the supernatant was kept in an ice-cold condition, the total protein concentration was measured by the Coomassie blue reaction (Coomassie Plus Protein Assay kit, Pierce Chemical Co, Rockford, IL). The supernatants were stored at –80°C until the Western blot analysis.

Western blot analysis.  Protein expressions of Mn-SOD and Cu/Zn-SOD in the supernatants were detected by Western blot analysis. In brief, the protein samples (50 µg/lane) were resolved by 12% SDS-PAGE and transferred to a nitrocellulose membrane with a semi-dry electroblotting apparatus (Transphor Electrophoresis Unit, Hoefer Scientific Instruments, San Francisco, CA). The membrane was blocked overnight at room temperature with a blocking buffer reagent (100 ml of 10x-TBS, containing 0.1% Tween 20, 50 g non-fat dry milk, and 1 g NaN3). Rabbit polyclonal anti-Mn-SOD (Upstate Biotechnology, Lake Placid, NY) and sheep polyclonal anti-Cu/Zn-SOD (Upstate Biotechnology) were used for immuno-blotting (both at 1:1,000 dilutions). The protein expression of ß-actin, as a marker for protein loading, was determined by using a mouse monoclonal anti-ß-actin antibody (Santa Cruz Biotechnology, Santa Cruz, CA) at 1:5,000 dilution. Secondary antibodies included peroxidase-linked species-specific sheep anti-mouse antibody, mouse anti-rabbit antibody, and donkey anti-sheep antibody (all from Santa Cruz Biotechnology) for monoclonal and polyclonal primary antibodies, respectively. The bands were detected by a chemiluminesent ECL kit (Pierce Chemical Co). The bands were measured with a computerized digital imaging system using Alpha-Image 2200 software (Alpha Innotech, San Leandro, CA). The Integrated Density Value (IDV) was obtained by integrating all of the pixel values in the area of one band after background correction.

Statistics.  Protein expression was reported as mean ± SD. Statistical comparisons of the tumor tissue and the surrounding tumor-free tissue from the same patient were performed by paired-sample t test. Values of p <0.05 were considered significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Breast tissue samples (n = 114) from the 57 patients were collected as paired specimens of tumor and tumor-free tissues. Immunoreactive Mn-SOD and Cu/Zn-SOD protein levels were examined by Western blot analysis of the proteins extracts from all of the 114 specimens.

Mn-SOD was identified in the Western blots of proteins extracted from breast tissues as a 24 kDa band, based upon immunoreactivity with rabbit antihuman Mn-SOD antibody (Fig. 1Go, panel A). The densitometric scan of each Mn-SOD band was expressed as a ratio to the corresponding scan of the ß-actin band in the Western blot, identified by immunoreactivity with mouse antihuman ß-actin antibody. The normalized densitometric scans of 57 paired Western blots showed that Mn-SOD protein expression in the breast tumors averaged 1.5-fold higher than in the corresponding tumor-free breast tissue (p <0.05) (Fig. 1Go, panel B).



View larger version (28K):
[in this window]
[in a new window]
  		Fig. 1. (Panel A): Typical Western blot to illustrate the expression of Mn-SOD protein in breast cancer tissue (lanes labeled B) compared to tumor-free breast tissue (lanes labeled N). Each pair of samples (N and B) was from a different patient. Tissue lysates were loaded (50 µg protein/lane) onto 12% SDS-PAGE gels, electrophoresed, and transferred to nitrocellulose membranes. The membranes were probed with an antibody for Mn-SOD and one for ß-actin (control).

(Panel B): Integrated density values (IDV) were obtained for each Mn-SOD protein band and expressed as a ratio to the IDV of the corresponding ß-actin band, after correction for background staining. The expression of Mn-SOD protein in extracts of 57 breast cancer tissues (column labeled B) was compared to that in extracts of 57 paired tumor-free breast tissues (column labeled N). The ratios of Mn-SOD to ß-actin levels were expressed as means ± SD. Mn-SOD expression in the breast cancers averaged 1.5-fold higher than in the tumor-free breast tissues (p <0.05).

 
Cu/Zn-SOD was identified in the Western blots of proteins extracted from breast tissues as a 16 kDa band, based upon immunoreactivity with the sheep antihuman Cu/Zn-SOD antibody (Fig. 2Go, panel A). The densitometric scan of each Cu/Zn-SOD band was expressed as a ratio to the corresponding scan of the ß-actin band in the Western blot, identified by immunoreactivity with mouse antihuman ß-actin antibody. Densitometric scans of 57 paired Western blots showed that Cu/Zn-SOD protein expression was approximately equal in the breast tumors and the corresponding tumor-free breast tissues (Fig. 2Go, panel B, no significant difference).



View larger version (26K):
[in this window]
[in a new window]
  		Fig. 2. (Panel A): Typical Western blot to illustrate the expression of Cu/Zn-SOD protein in breast cancer tissue (lanes labeled B) compared to tumor-free breast tissue (lanes labeled N). Each pair of samples (N and B) was from a different patient. Tissue lysates were loaded (50 µg protein/lane) onto 12% SDS-PAGE gels, electrophoresed, and transferred to nitrocellulose membranes. The membranes were probed with an antibody for Cu/Zn-SOD and one for ß-actin (control).

(Panel B): Integrated density values (IDV) were obtained for each Cu/Zn-SOD protein band and expressed as a ratio to the IDV of the corresponding ß-actin band, after correction for background staining. The expression of Cu/Zn-SOD protein in extracts of 57 breast cancer tissues (column labeled B) was compared to that in extracts of 57 paired tumor-free breast tissues (column labeled N). The ratios of Cu/Zn-SOD to ß-actin levels were expressed as means ± SD. The mean CuZn-SOD expression in the breast cancers did not differ significantly from that in the tumor-free breast tissues.

 
No statistically significant associations were observed between the Mn-SOD and Cu/Zn-SOD protein expression levels in neoplastic breast tissues and any of the demographic or clinical categories. In respect to the pathological stages of the breast cancers, 79% were at stage II, whereas only 12% and 9% were at stages I and III, respectively. These data were inadequate to determine if up-regulation of Mn-SOD protein expression in breast cancer tissues was significantly related to the tumor stage.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Carcinogenesis is a process with at least three stages including initiation, promotion, and malignant conversion[19]. Oxidative DNA damage, including mutagenic and cytotoxic lesions, is implicated in the initiation phase of carcinogenesis. The interaction between oxygen-radicals and DNA produces base adducts, deletions, frameshifts, strands breaks, and DNA-protein crosslinks [20]. Defective repair of DNA lesions leads to mutations, blocking of replication and transcription, and chromosomal aberrations [19,21]. Oxygen free radicals attack breast epithelium and lead to fibroblast proliferation, epithelial hyperplasia, cellular atypia, and breast cancer [22]. Antioxidant enzymes and oxidant detoxifiers can inhibit tumor initiation and promotion in vivo and in vitro [19,23].

Oytun et al [24] reported that Mn-SOD and total SOD enzymatic activities in breast tumor tissues were significantly higher than those in the corresponding cancer-free tissues [24]. Oberley and coauthors [25,26] observed that total and mitochondrial SOD activities were increased in human tumor cell lines. Ray et al [27] found that erythrocyte SOD activity was increased in breast cancer patients [27]. Izutani et al [28] noted increased Mn-SOD mRNA expression in tumor tissues from patients with gastric carcinoma compared to normal gastric mucosa [28]. Li et al [29] reported that Mn-SOD activity correlated with the degree of differentiation of human breast cancer cells.

In general, overexpression of cytokines (eg, TNF-{alpha}, IL-1ß, or IFN-{gamma}) is observed in tumors, including renal cell carcinoma [30], gastrointestinal tumors [31], and lymphomas [32]. Mallmann et al [33] showed that the expression of various cytokines in patients with breast cancer is different from those without breast cancer. Voldko and Bulinskii [34] observed that a specific cytokine, TNF-{alpha}, was elevated in serum from individuals with breast cancer compared to controls. Harris et al [35] showed that TNF-{alpha} induced Mn-SOD expression in various cell lines, including human MCF-7 breast adenocarcinoma cells. Similarly, TNF-{alpha} increased Mn-SOD activity and mRNA in a dose- and time-dependent manner in MCF-7 cells [36]. The present authors suggest that the elevation of Mn-SOD expression in breast cancers may reflect the concentrations of serum TNF-{alpha} in breast cancer patients.

Increased SOD produces higher H2O2, which is normally detoxified by catalase or glutathione peroxidase. Catalase is a primary antioxidant defense that converts H2O2 to water. The catalase activity in breast cancer tissues and in serum of breast cancer patients is lower than in controls [27,37]. Decreased catalase activity in tumor cells leads to accumulation of H2O2, which causes DNA damage or cell death. The combination of elevated Mn-SOD activity and decreased catalase activity in breast tumors may enhance the frequency of mutations and lead to neoplastic transformation.

Mn-SOD has an essential role in the conversion of superoxide anion to H2O2 in the mitochondrial matrix [38] and is a key factor in cell survival [39]. Mn-SOD is a determinant of cellular resistance to pro-oxidant cytokines and contributes to the survival of cells exposed to ionizing radiation and tumoricidal chemotherapeutic drugs [40]. Peng Huang et al [41] suggest that inhibition of SOD causes accumulation of cellular O2–•, which leads to free-radical-mediated damage to mitochondrial membranes, a process that releases of cytochrome c from mitochondria and induces apoptosis of cancer cells. On the other hand, Lu et al [42] reported that cancer cells can escape recognition by cytotoxic lymphocytes if the activities of antioxidant enzymes are increased [42].

Development of breast cancer is frequently followed by inflammation of the breast. Studies in mouse models of mammary tumorigenesis and in human breast cancer cells indicate that COX-2, an inducible form of cyclooxygenase, plays an important role in the pathogenesis of breast cancer in humans [43]. In response to the subsequent local inflammation and/or proinflammatory cytokines, Mn-SOD expression may become elevated and may function as an anti-apoptotic factor, allowing selective accumulation of cells with an increased mutation frequency and immortality. Increased Mn-SOD expression may also contribute a growth advantage to tumor cells over their normal counterparts.

Further research is needed to delineate the roles of Mn-SOD in breast cancer, to identify the signaling pathways that regulate the expression of Mn-SOD in breast tissue, and to determine whether Mn-SOD expression in biopsy specimens can serve as a prognostic marker of breast cancer.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Parkin DM, Pisani P, Ferlay J. Estimation of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999; 80:827–841.[Medline]
  2. WHO. The World Health Report, Geneva: WHO, 1997.
  3. Cancer Registry Annual Report (1999), Republic of China. Department of Health, the Executive Yuan. ROC. April 2003.
  4. Hou MF, Tsai KB, Fan HM, Wang CY, Lin WC, Liu CS, Lin HJ, Chai CY, Ou-Yang F, Li SSL, Chang YY, Huang TJ. Familial breast cancer in Southern Taiwan. Kaohsiung J Med Sci 2000;16:414–421.[Medline]
  5. Russo J, Fu Hu Y, Yang X, Russo IH. Development, cellular, and molecular basis of human breast cancer. J Natl Cancer Inst Monogr 2000;27:17–37.
  6. Clemons M, Goss P. Estrogen and the risk of breast cancer. NEJM 2001;344:276–85.[Free Full Text]
  7. Carter RF. BRCA1, BRCA2 and breast cancer: a concise clinical review. Clin Invest Med 2001;24:147–157.[Medline]
  8. Li SSL, Tseng HM, Yang TP, Liu CH, Teng SJ, Huang HW, Chen LM, Kao HW, Chen JH, Tseng JN, Chen A, Hou MF, Huang TJ, Chang JH, Mok KT, Tsai JH. Molecular characterization of germline mutations in BRCA1 and BRCA2 genes from breast cancer families in Taiwan. Hum Genet 1999;104:201–204.[Medline]
  9. Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human diseases: an overview. Methods Enzymol 1989;186:1–85.
  10. Halliwell B. Free radicals, antioxidants, and human disease. Curiosity, cause, or consequence? Lancet 1994; 344:721–724.[Medline]
  11. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, 3rd ed, Oxford Univ Press, Oxford, 1999.
  12. Wong GHW. Protective roles of cytokines against radiation: Induction of mitochondrial MnSOD. Biochim Biophys Acta 1995;1271:205–209.[Medline]
  13. Crapo JD, Tierney DF. Superoxide dismutase and pulmonary oxygen toxicity. Am J Physiol 1974;226:1401–1407.[Free Full Text]
  14. Oberley LW, St Clair DK, Oberley TD. Increase in manganese superoxide dismutase activity in the mouse heart after X-irradiation. Arch Biochem Biophys 1987; 254:69–80.[Medline]
  15. Wong GH, Goeddel DV. Induction of manganese super-oxide dismutase by tumor necrosis factor: possible protective mechanism. Science 1988;242:941–944.[Abstract/Free Full Text]
  16. Warner BB, Stuart L, Gebb S, Wispe JR. Redox regulation of manganese superoxide dismutase. Am J Physiol 1996; 271:L150–158.
  17. Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S. Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clin Chim Acta 2002;325:165–170.[Medline]
  18. Kumaraguruparan R, Subapriya R, Kabalimoorthy J, Nagini S. Antioxidant profile in the circulation of patients with fibroadenoma and adenocarcinoma of the breast. Clin Biochem 2002;35:275–279.[Medline]
  19. Guyton KZ, KenSler TW. Oxidative mechanism in carcinogenesis. Br Med Bull 1993;49:523–544.[Abstract/Free Full Text]
  20. McCord JM. Human disease, free radicals and the oxidant/antioxidant balance. Clin Biochem 1993;26:351–357.[Medline]
  21. Sodum RS. Steroselective formation of in vitro nucleic acid adducts by 2,3-epoxy-4-hydroxy. Cancer Res 1991; 51:137–143.[Abstract/Free Full Text]
  22. Hochstein P, Atallah A. The nature of oxidants and anti-oxidant systems in the inhibition of mutation and cancer. Mut Res 1988;202:363–335.[Medline]
  23. O’ Brien PJ. Antioxidants and cancer. Molecular mechanism in medicine. In: Free Radicals in Diagnosis (Armstrong D, Ed) Plenum Press, New York, 1994; pp. 215–239.
  24. Oytun P, Ozay O, Mine EI, Berrin B, Muberra K, Iskender S. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochemistry 2000;33:279–284.
  25. Liu R, Oberley LW. Transfection and expression of MnSOD cDNA decreases tumor malignancy of human oral squamous carcinoma SCC-25 cells. Hum Gene Ther 1997;8:585–595.[Medline]
  26. Zhong W, Oberley LW. Suppression of the malignant phenotype of human glioma cells by overexpression of MnSOD. Oncogene 1997;4:481–490.
  27. Ray G, Batras S, et al. Lipid peroxidation, free radical production and antioxidant ststus in tissues of breast cancer. Breast Cancer Res Treat 2000;59:163–170.[Medline]
  28. Izutani R, Katoh M, Asano S. Enhanced expression of manganese superoxide dismutase mRNA and increased TNF and mRNA expression by gastric mucosa and gastric cancer. World J Surg 1996;20:228–233.[Medline]
  29. Li JJ, Oberley LW, St Clair DK, Ridnucr LA, Oberley TD. Phenotypic changes induced in human breast cancer cells by overexpression of manganese-containing superoxide dismuatase. Oncogene 1995;10:1989–2000.[Medline]
  30. Ikemoto S, Sugimura K, Yoshida N, Wada S, Yamamoto K, Kishimoto T. TNF-{alpha}, Il-ß and IL-6 production by peripheral blood monocytes in patients with renal cell carcinoma. Anticancer Res 2000;20:317–322.[Medline]
  31. Bossala M, Muscaritoli M, Bellantone R, Pacelli F, Casino A, Sgadari A, Abttaglia F, Piccioni E, Scambia G, Doglietto GB. Serum tumor necrosis factor-{alpha} mRNA levels in cancer patients are discontinuous and correlate with weight loss. Eur J Clin Investig 2000;30:1107–1112.[Medline]
  32. Baseggio L, Bienvenum J, Charlot C, Picollet J, Felman P, Ooiffier B, Salles G. Higher LPS-stimulated TNF-{alpha} mRNA levels in peripheral blood mononuclear cells from non-Hodgkin’s lymphoma patients. Exp Haematol 2001; 29:330–338.[Medline]
  33. Mallmann P, Diedrich K, Mallmann R, Koenig MD, Krebs D. Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leukocyte migration inhibition test in breast cancer patients. Anticancer Res 1991;11:1509–1513.[Medline]
  34. Voldko NA, Bulinskii BT. Evaluation of tumor necrosis factor (TNF) in cancer patients. Vopr Oncol 1994;40: 181–185.
  35. Harris CA, Derbin KS et al. Manganese superoxide dismutase is induced by IFN-{alpha} tumor necrosis factor or IL-1. J Immunol 1991;147:149–154.[Abstract]
  36. Linda M, Jeanne M and Margaret M. Antioxidant defenses in TNF-treated MCF-7 cells: selective increase in MnSOD. Free Rad Bio Med 1999;26:919–924[Medline]
  37. Punnonen K, Ahotupa M, Asaishi, Hyoty M, Kudo K. Antioxidant enzyme activities and oxidative stress in human breast cancer. J Cancer Res Clin Oncol 1994;120: 374–377.[Medline]
  38. Selman MD, Quirk WS, Shirwany NA. Reactive oxygen metabolites, antioxidants and head and neck cancer. Head Neck 1999;21:467–479.[Medline]
  39. Hirose K, Longo DL, Oppenheim JJ, Matsushima K. Overexpression of mitochondrial manganese superoxide diamutase promotes the survival of tumor cells exposed to interleukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation. FASEB J 1993;7:361–368.[Abstract]
  40. Kuninak S, Ichinose Y, Koja K and Toh Y. Suppression of mitochondrial manganese superoxide dismutase augments sensitivity to radiation, hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis. Br J Cancer 2000;83: 928–924.[Medline]
  41. Peng Huang, Li Feng, Elizabeth AO, Micheal JK, William P. Superoxide dismutase as a target for the selective killing of cancer cells. Nature 2000;407:390–395.[Medline]
  42. Lu YP, Lou YR, Yen P, Newmark HL, Mirochnitchenka OI, Inouye M. Enhanced skin carcinogenesis in transgenic mice with high expression of glutathione peroxidase or both glutathione peroxide and superoxide dismutase. Cancer Res 1997;57:1468–1474.[Abstract/Free Full Text]
  43. Singh B, Lucci A. Role of cyclooxygenase in breast cancer. J Surg Res 2002;108:173–179.[Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Er, T.-K.
Right arrow Articles by Tsai, L.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Er, T.-K.
Right arrow Articles by Tsai, L.-Y.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS