Pharmacological inhibition of fatty acid synthase (FAS): A novel therapeutic approach for breast cancer chemoprevention through its ability to suppress Her-2/neu (erbB-2) oncogene-induced malignant transformation

Molecular Carcinogenesis

Volumn 41, Issue 3, 2004, Pages 164-178

  Menendez, Javier A ^a,b   Mehmi, Inderjit ^a   Verma, Vishal A ^a   Teng, Poh K ^a   Lupu, Ruth ^a,b,c  

^a Breast Cancer Translational Res Lab   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

^c Evanston NW Hlthcare Res Institute ^*  (United States)

Author keywords

Apoptosis; C75; Cerulenin; Chemoprevention; erbB 2; Fatty acid synthase; Her 2 neu; Transformation

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 MORPHOLINO 8 PHENYLCHROMONE; CERULENIN; DNA FRAGMENT; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FAS ANTIGEN; FATTY ACID SYNTHASE; HISTONE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANIMAL CELL; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER GROWTH; CELL VIABILITY; CHEMOPROPHYLAXIS; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME LINKED IMMUNOSORBENT ASSAY; FIBROBLAST; GENE OVEREXPRESSION; GENE SEQUENCE; GENETIC CODE; GENETIC ENGINEERING; MOUSE; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UPREGULATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; 4-BUTYROLACTONE; ANIMALS; ANTIBIOTICS, ANTIFUNGAL; ANTIGENS, CD95; APOPTOSIS; BREAST NEOPLASMS; CELL ADHESION; CELL TRANSFORMATION, NEOPLASTIC; CELLS, CULTURED; CERULENIN; CHEMOPREVENTION; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FATTY ACID SYNTHETASE COMPLEX; FATTY ACIDS; FIBROBLASTS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IN SITU NICK-END LABELING; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; NIH 3T3 CELLS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, ERBB-2; RECEPTORS, TUMOR NECROSIS FACTOR;

EID: 7244252915     PISSN: 08991987     EISSN: None     Source Type: Journal    
DOI: 10.1002/mc.20054     Document Type: Article

References (64)

1. Kuhajda FP. Fatty-acid synthase and human cancer: New perspectives on its role in tumor biology. Nutrition 2000;16:202-208.
2. Wakil SJ. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 1989;28:4523-4530.
3. Kuhajda FP, Jenner K, Wood FD, et al. Fatty acid synthesis: A potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 1994;91:6379-6383.
4. Pizer ES, Jackisch C, Wood FD, Pasternack GR, Davidson NE, Kuhajda FP. Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 1996;56:2745-2747.
5. Pizer ES, Thupari J, Han WF, et al. Malonyl-coenzyme A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 2000;60:213-218.
6. Kuhajda FP, Pizer ES, Li JN, Mani NS, Frehywot GL, Townsend CA. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci USA 2000;97:3450-3454.
7. Zhou W, Simpson PJ, McFadden JM, et al. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res 2003;63:7330-7337.
8. Pizer ES, Pflug BR, Bova GS, Han WF, Udan MS, Nelson JB. Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression. Prostate 2001;47:102-110.
9. Epstein JI, Carmichael M, Partin AW. OA-519 (fatty acid synthase) as an independent predictor of pathological state in adenocarcinoma of the prostate. Urology 1995:n 45:81-86.
10. Bull JH, Ellison G, Patel A, et al. Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br J Cancer 2001;84:1512-1519.
11. Kusakabe T, Nashimoto A, Honma K, Suzuki T. Fatty acid synthase is highly expressed in carcinoma, adenoma, and in regenerative epithelium and intestinal metaplasia of the stomach. Histopathology 2002;40:71-79.
12. Nemoto T, Terashima S, Kogure M, et al. Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology 2001;69:297-303.
13. Krontiras H, Roye GD, Beenken SE, et al. Fatty acid synthase expression is increased in neoplastic lesions of the oral tongue. Head Neck 1999;21:325-329.
14. Rashid A, Pizer ES, Moga M, et al. Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 1997;150:201-208.
15. Visca P, Alo PL, Del Nonno F, et al. Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa. Clin Cancer Res 1999;5:4111-4118.
16. Milgraum LZ, Witters LA, Pasternack GR, Kuhajda FP. Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res 1997;3:2115-2120.
17. Alo PL, Visca P, Botti C, et al. Immunohistochemical expression of human erythrocyte glucose transporter and fatty acid synthase in infiltrating breast carcinomas and adjacent typical/atypical hyperplastic or normal breast tissue. Am J Clin Pathol 2001;116:129-134.
18. DiGiovanna MP, Chu P, Davison TL, et al. Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: Clinicopathological correlates. Cancer Res 2002;62:6667-6673.
19. Xu R, Perle MA, Inghirami G, Chan W, Delgado Y, Feiner H. Amplification of Her-2/neu in Her-2/neu-overexpressing and nonexpressing breast carcinomas and their synchronous benign, premalignant, and metastatic lesions detected by FISH in archival material. Modern Pathol 2002;15:116-124.
20. Hoque A, Sneige N, Sahin AA, et al. HER-2/neu gene amplification in ductal carcinoma in situ of the breast. Cancer Epidemiol Biomarkers Prev 2002;11:587-590.
21. Kumar-Sinha C, Ignatoski KW, Lippman ME, Ethier SP, Chinnaiyan AM. Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Res 2003;63:132-139.
22. Menendez JA, Mehmi I, Atlas E, Colomer R, Lupu R. Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acid, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB. Int J Oncol 2004;24:591-608.
23. Menendez JA, Lupu R, Colomer R. Inhibition of tumor-associated fatty acid synthase hyperactivity induces synergistic chemosensitization of HER-2/neu-overexpressing human breast cancer cells to docetaxel (taxotere). Breast Cancer Res Treat 2004;84:183-195.
24. Omura S. The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev 1976;40:681-697.
25. Vance D, Goldberg I, Mitsuhashi O, Bloch K. Inhibition of fatty acid synthethases by the antibiotic cerulenin. Biochem Biophys Res Commun 1972;48:549-565.
26. Christie WW, Hunter ML, Clegg RA. The effects of cerulenin on lipid metabolism in vitro in cellular preparation from the rat. Biochim Biophys Acta 1981;666:284-290.
27. Moche M, Schneider G, Edwards P, Dehesh K, Lindqvist Y. Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl carrier protein synthase. J Biol Chem 1999;274:6031-6034.
28. Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 1987;237:178-182.
29. Hudziak RM, Schlessinger J, Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci USA 1987;84:7159-7163.
30. Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S, Arteaga CL. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 2002;62:4132-4141.
31. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2:127-137.
32. Kurokawa H, Arteaga CL. Inhibition of erbB (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. Clin Cancer Res 2001;7(Suppl):4436s-4442s.
33. Pizer ES, Wood FD, Pasternack GR, Kuhajda FP. Fatty acid synthase (FAS): A target for cytotoxic antimetabolites in HL60 promyelocytic leukemia cells. Cancer Res 1996;56:745-751.
34. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J 2000;19:3159-3167.
35. Thompson BJ, Stern A, Smith S. Purification and properties of fatty acid synthase from a human breast cancer cell line. Biochem Biophys Acta 1981;662:125-130.
36. Thompson BJ, Smith S. Lack of coordinated regulation of lipogenic enzymes using a human breast cancer cell line, SKBr3. Biochem Biophys Acta 1982;712:217-220.
37. Menendez JA, Vellon L, Mehmil, et al. Inhibition of fatty acid synthase (FAS) suppresses HER-2/neu (erbB-2) oncogene overexpression in cancer cells. Proc Natl Acad Sci USA 2004); doi/10.1073/pnas.0403390101.
38. Hsu DK, Donohue PJ, Alberts GF, Winkles JA. Fibroblast growth factor-1 induces phosphofructokinase, fatty acid synthase and Ca(2+)-ATPase mRNA expression in NIH 3T3 cells. Biochem Biophys Res Commun 1993;197:1483-1491.
39. Yang Y-A, Han WF, Morin PJ, Chrest FJ, Pizer ES. Activation of fatty acid synthesis during neoplastic transformation: Role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp Cell Res 2002;279:80-90.
40. Van de Sande T, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV. Role of the phosphatidylinositol 3′-kinase/PTEN/ Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Res 2002;62:642-646.
41. Wang D, Sul HS. Insulin stimulation of the fatty acid synthase promoter is mediated by the phosphatidylinositol 3-kinase pathway. Involvement of protein kinase B/Akt. J Biol Chem 1998;273:25420-25426.
42. Swinnen JV, Heemers H, Deboel L, Foufelle F, Heyns W, Verhoeven G. Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway. Oncogene 2000;19:5173-5181.
43. Li JN, Mahmoud MA, Han WF, Ripple M, Pizer ES. Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia. Exp Cell Res 2000;261:159-165.
44. Yang Y-A, Morin PJ, Han WF, et al. Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein 1-c. Exp Cell Res 2003;282:132-137.
45. Kim JB, Sarraf P, Wright M, et al. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 1998;101:1-9.
46. Shimano H, Yahagi N, Amemiya-Kudo M, et al. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional regulation of lipogenic enzymes genes. J Biol Chem 1999;274:35832-35839.
47. Kotzka J, Muller-Wieland D, Roth G, et al. Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade. J Lipid Res 2000;41:99-108.
48. Fleischmann M, Lynedjian PB. Regulation of sterol regulatory-element binding protein 1 gene expression in liver: Role of insulin and protein kinase B/cAkt. Biochem J 2000;349:13-17.
49. Ookhtens M, Kannan R, Lyon I, Baker N. Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 1984;247:R146-R153.
50. Sabine JR, Abraham S, Chaikoff IL. Control of lipid metabolism in hepatomas: Insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res 1967;27:793-799.
51. Xing X, Wang SC, Xia W, et al. The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis. Nat Med 2000;6:189-195.
52. Wang SC, Hung MC. Transcriptional targeting of the HER-2/ neu oncogene. Drugs Today (Barc) 2000;36:835-843.
53. Baert JL, Monte D, Musgrove EA, Albagli O, Sutherland RL, de Launoit Y. Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells. Int J Cancer 1997;70:590-597.
54. Swinnen JV, van Veldhoven PP, Timmermans L, et al. Fatty acid synthase drives the synthesis of phospholipids into detergent-resistant membrane microdomains. Biochem Biophys Res Commun 2003;302:898-903.
55. Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997;387:569-572.
56. Janes PW, Ley SC, Magee AI. Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. J Cell Biol 1999;147:447-461.
57. Pike LJ. Lipid rafts: bringing order to chaos. J Lipid Res 2003;44:655-667.
58. Harder T, Scheiffele P, Verkade P, Simons K. Lipid domain structure of the plasma membrane revealed by patching of membrane components. J Cell Biol 1998;141:929-942.
59. Nagy P, Bene L, Balázs M, et al. EGF-induced redistribution of erbB2 on breast tumor cells: Flow and image cytometric energy transfer measurements. Cytometry 1998;32:120-131.
60. Nagy P, Vereb G, Sebestyen Z, et al. Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2. J Cell Sci 2002;115:4251-4262.
61. DiGiovanna MP. Clinical significance of HER-2/neu overexpression. Part I. In: Vita De VT Jr, Hellman S, Rosenberg SA, editors. Principles and Practice of Oncology. Vol. 13: No. 9. Cedar Nolls: Lippincott Williams & Wilkins; 1999.
62. DiGiovanna MP. Clinical significance of HER-2/neu overexpression. Part II. In: Vita De VT Jr, Hellman S, Rosenberg SA, editors. Principles and Practice of Oncology. Vol. 13: No. 10. Cedar Nolls: Lippincott Williams & Wilkins; 1999.
63. Menendez JA, Colomer R, Lupu R. Inhibition of tumor-associated fatty acid synthase activity enhances vinorelbine (Navelbine®)-induced cytotoxicity and apoptotic cell death in human breast cancer cells. Oncol Rep 2004;12:411-422.
64. Moasser MM, Basso A, Averbuch SD, Rosen N. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001;61:7184-7188.