Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: From anabolic-energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells

Archivum Immunologiae et Therapiae Experimentalis

Volumn 52, Issue 6, 2004, Pages 414-426

  Menendez, Javier A ^a,b   Lupu, Ruth ^a,b,c  

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

^b NORTHWESTERN UNIVERSITY   (United States)

^c Ctr on Outcomes Res and Education   (United States)

Author keywords

Cancer; Fatty acid synthase; Fatty acids; Metabolism; Oncogene

Indexed keywords

DOCETAXEL; FATTY ACID SYNTHASE; NAVELBINE; PACLITAXEL; TAXANE DERIVATIVE; TRASTUZUMAB;

APOPTOSIS; BIOSYNTHESIS; BREAST CANCER; CANCER; CANCER CELL; CANCER CELL DESTRUCTION; CATALYSIS; CELL PROLIFERATION; CELL SURVIVAL; CHEMOTHERAPY; DOWN REGULATION; ENERGY; ENZYME ANALYSIS; EPIGENETICS; FAT INTAKE; FATTY ACID METABOLISM; FATTY ACID SYNTHESIS; GENE EXPRESSION; GRAFT SURVIVAL; HUMAN; HYPERACTIVITY; HYPOXIA; NUTRITION; ONCOGENE; ONCOGENE NEU; PHENOTYPE; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SENSITIVITY ANALYSIS;

EID: 12344278357     PISSN: 0004069X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (120)

1. Alaoui-Jamali M. A., Paterson J., Al Moustafa A. E. and Yen L. (1997): The role of ErbB-2 tyrosine kinase receptor in cellular intrinsic chemoresistance: mechanisms and implications. Biochem. Cell Biol., 75, 315-325.
2. Albanell J. and Baselga J. (2001): Unrevealing resistance to trastuzumab (Herceptin): insulin-like factor-1 receptor, a new suspect. J. Natl. Cancer Inst, 93, 1830-1832.
3. Alo P. L., Visca P., Botti C., Galati G. M., Sebastiani V., Andreano T., Di Tondo U. and Pizer E. S. (2001): 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., 116, 129-134.
4. Alo P. L., Visca P., Marci A., Mangoni A., Botti C. and Di Tondo U. (1996): Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer, 77, 474-482.
5. Alo P. L., Visca P., Trombetta G., Mangoni A., Lenti L., Monaco S., Botti C., Serpieri D. E. and Di Tondo U. (1999): Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas. Tumori, 85, 35-40.
6. Baron A., Migita T., Tang D. and Loda M. (2004): Fatty acid synthase: a metabolic oncogene in prostate cancer? J. Cell. Biochem., 91, 47-53.
7. (R) (trastuzumab). Eur. J. Cancer, 37, 18-24.
8. Baselga J., Norton L., Albanell J., Kim Y. M. and Mendelshon J. (1998): Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2-neu overexpressing human breast cancer xenografts. Cancer Res., 58, 2825-2831.
9. Begin M. E., Das U. N. and Ells G. (1986): Cyto-toxic effects of essential fatty acids (EFA) in mixed cultures of normal and malignant human cells. Prog. Lipid Res., 25, 573-576.
10. Begin M. E., Das U. N. and Horrobin D. F. (1986): Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. J. Natl. Cancer Inst., 77, 1053-1062.
11. Begin M. E., Ells G. and Horrobin D. F. (1988): Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. J. Natl. Cancer Inst., 80, 188-194.
12. Bougnoux P., Koscielny S., Chajes V., Descamps P., Couet C. and Calais G. (1994): α-Linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Br. J. Cancer, 70, 330-334.
13. Brown J. M. and Giaccia A. J. (1998): The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res., 58, 1408-1416.
14. Bull J. H., Ellison G., Patel A., Muir G., Walker M., Underwood M., Khan F. and Paskins L. (2001): Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br. J. Cancer, 84, 1512-1519.
15. Camassei F. D., Jenkner A., Rava L., Bosman C., Francalanci P., Donfrancesco A., Alo P. L. and Boldrini R. (2003): Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma: an interinstitutional study. Med. Pediatr. Oncol., 40, 302-308.
16. Carter P., Presta L., Gorman C. M., Ridgway J. B., Henner D., Wong W. L., Rowland A. M., Kotts C., Carver M. E. and Shepard H. M. (1992): Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl. Acad. Sci. USA, 89, 4285-4289.
17. Chalbos D., Joyeux C, Galtier F. and Rochefort H. (1992): Progestin-induced fatty acid synthetase in human mammary tumors: from molecular to clinical studies. Steroid Biochem. Mol. Biol., 43, 223-228.
18. Chirala S. S., Jayakumar A., Gu Z. W. and Wakil S. (2001): Human fatty acid synthase: role of interdomain in the formation of catalytically active synthase dimer. Proc. Natl. Acad. Sci. USA, 98, 3104-3108.
19. Christie W. W., Hunter M. L. and Clegg R. A. (1981): The effects of cerulenin on lipid metabolism in vitro in cellular preparation from the rat. Biochim. Biophys. Acta, 666, 284-290.
20. Clarke B. A., Armstrong M. K. and Jump D. B. (1990): Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance. J. Nutr., 120, 218-224.
21. Clarke S. D. (1993): Regulation of fatty acid synthase gene expression: an approach for reducing fat accumulation. J. Anim. Sci., 71, 1957-1965.
22. Cobleigh M. A., Vogel C. L., Tripathy D., Robert N. J., Scholl S., Fehrenbacher L., Wolter J. M., Paton V., Shak S., Lieberman G. and Slamon D. J. (1999): Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER-2 overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol., 17, 2639-2648.
23. De Schrijver E., Brusselmans K., Heyns W., Verhoeven G. and Swinnen J. V. (2003): RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Res., 63, 3799-3804.
24. Deng X., Cagen L. M., Wilcox H. G., Park E. A., Raghow R. and Elam M. B. (2002): Regulation of the rat SREBP-1c promoter in primary rat hepatocytes. Biochem. Biophys. Res. Commun., 290, 256-262.
25. Epstein J. I., Carmichael A. and Partin A. W. (1995): OA-519 (fatty acid synthase) as an independent predictor of pathologic stage in adenocarcinoma of the prostate. Urology, 45, 81-86.
26. Escot C., Joyeux C., Mathieu M., Maudelonde T., Pages A., Rochefort H. and Chalbos D. (1990): Regulation of fatty acid synthetase ribonucleic acid in the human endometrium during the menstrual cycle. J. Clin. Endocrinol. Metab., 70, 1319-1324.
27. Favoni R. E. and de Cupis A. (1998): Steroidal and nonsteroidal oestrogen antagonists in breast cancer: basic and clinical appraisal. Trends Pharmacol. Sci., 19, 406-415.
28. Fleischmann M. and Iynedjian P. B. (2000): Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt. Biochem. J., 349, 13-17.
29. Fukuda H., Iritani N., Sugimoto T. and Ikeda H. (1999): Transcriptional regulation of fatty acid synthase by insulin/glucose, polyunsaturated fatty acids and leptin in hepatocytes and adipocytes in normal and genetically obese rats. Eur. J. Biochem., 260, 505-511.
30. Gabrielson E. W., Pinn M. L., Testa J. R. and Kuhajda F. P. (2001): Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin. Cancer Res., 7, 153-157.
31. rd, Hunt D. A., Schaffel S. and Hennigar R. A. (1997): Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum. Pathol., 28, 686-692.
32. Heemers H., Maes B., Foufelle F., Heyns W., Verhoeven G. and Swinnen J. V. (2001): Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway. Mol. Endocrinol., 15, 1817-1828.
33. Hochachka P. W. (1980): Living without oxygen. Harvard University Press, Cambridge, MA, USA, 1-181.
34. Hochachka P. W., Rupert J. L., Goldenberg L., Gleave M. and Kozlowski P. (2002): Going malignant: the hypoxia-cancer connection in the prostate. Bioessays, 24, 749-757.
35. Horrobin D. F. (1989): Polyunsaturated fatty acids and human cancer. In Abraham S. (ed.): Carcinogenesis and dietary fat. Kluwer Academic Publishers, Boston, 247-262.
36. Horrobin D. F. (1990): Essential fatty acids, lipid peroxidation, and cancer. In Horrobin D. F. (ed.): Omega-6 essential fatty acids. Wiley-Liss, New York, 351-378.
37. Horrobin D. F. (1994): Unsaturated lipids and cancer. In Horrobin D. F. (ed.): New approaches to cancer treatment. Churchill, Edinburgh, 1-29.
38. Innocenzi D., Alo P. L., Balzani A., Sebastiani V., Silipo V., La Torre G., Ricciardi G., Bosman C. and Calvieri S. (2003): Fatty acid synthase expression in melanoma. J. Cutan. Pathol., 30, 23-28.
39. Jensen V., Ladekari M., Holm-Nielsen P., Flemming B. S. and Fleming M. (1995): The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node negative breast cancer. J. Pathol., 176, 343-352.
40. Jiang W. G., Bryce R. P. and Horrobin D. F. (1998): Essential fatty acids: molecular basis of their anti-cancer action and clinical implications. Crit. Rev. Oncol. Hematol., 27, 179-209.
41. Joyeux C., Rochefort H. and Chalbos D. (1989): Progestin increases gene transcription and messenger ribonucleic acid stability of fatty acid synthetase in breast cancer cells. Mol. Endocrinol., 3, 681-686.
42. Kalkhoven E., Kwakkenbos-Isbrucker L., de Laat S. W., van der Saag P. T. and van der Burg B. (1994): Synthetic progestins induce proliferation of breast tumor cell lines via the progesterone or estrogen receptor. Mol. Cell. Endocrinol., 102, 45-52.
43. Katsurada A., Iritani N., Fukuda H., Matsumara Y., Nishimoto N., Noguchi T. and Tanaka T. (1990): Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver. Eur. J. Biochem., 190, 427-433.
44. Kersten S. (2001): Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep., 2, 282-286.
45. Kim J. B., Sarraf P., Wright M., Yao K. M., Mueller E., Solanes G., Lowell B. B. and Spiegelman B. M. (1998): Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J. Clin. Invest., 101, 1-9.
46. Klein V., Chajes V., Germain E., Schulgen G., Pinault M., Malvy D., Lefrancq T., Fignon A., Le Floch O., Lhuillery C. and Bougnoux P. (2000): Low α-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer. Eur. J. Cancer, 36, 335-340.
47. Kotzka J., Muller-Wieland D., Roth G., Kremer L., Munck M., Schurmann S., Knebel B. and Krone W. (2000): Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade. J. Lipid Res., 41, 99-108.
48. Krontiras H., Roye G. D., Beenken S. E., Myers R. B., Mayo M. S., Peters G. E. and Grizzle W. E. (1999): Fatty acid synthase expression is increased in neoplastic lesions of the oral tongue. Head Neck, 21, 325-329.
49. Kuhajda F. P. (2000): Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition, 16, 202-208.
50. Kuhajda F. P., Jenner K., Wood F. D., Hennigar R. A., Jacobs L. B., Dick J. D. and Pasternack G. R. (1994): Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc. Natl. Acad. Sci. USA, 91, 6379-6383.
51. Kuhajda F. P., Katumuluwa A. I. and Pasternack G. R. (1989): Expression of haptoglobin-related protein and its potential as a tumor antigen. Proc. Natl. Acad. Sci. USA, 86, 1188-1192.
52. Kuhajda F. P., Piantadosi S. and Pasternack G. P. (1989): Haptoglobin-related protein (Hpr) epitopes in breast cancer as a predictor of recurrence of the disease. N. Engl. J. Med., 321, 636-641.
53. Kuhajda F. P., Pizer E. S., Li J. N., Mani N. S., Frehywot G. L. and Townsend C. A. (2000): Synthesis and anti-tumor activity of a novel inhibitor of fatty acid synthase. Proc. Natl. Acad. Sci. USA, 97, 3450-3454.
54. Kumar-Sinha C., Ignatoski K. W., Lippman M. E., Ethier S. P. and Chinnaiyan A. M. (2003): Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Res., 63, 132-139.
55. Kusakabe T., Maeda M., Hoshi N., Sugino T., Watanabe K., Fukuda T. and Suzuki T. (2000): Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells. J. Histochem. Cytochem., 48, 613-622.
56. Kusakabe T., Nashimoto A., Honma K. and Suzuki T. (2002): Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach. Histopathology, 40, 71-79.
57. Li J. N., Gorospe M., Chrest F. J., Kumaravel T. S., Evans M. K., Han W. F. and Pizer E. S. (2001): Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53. Cancer Res., 61, 1493-1499.
58. Li J. N., Mahmoud M. A., Han W. F., Ripple M. and Pizer E. S. (2000): Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia. Exp. Cell Res., 261, 159-165.
59. Magana M. M. and Osborne T. F. (1996): Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. J. Biol. Chem., 271, 32689-32694.
60. Maillard V., Bougnoux P., Ferrari P., Jourdan M. L., Pinault M., Lavillonniere F., Body F., Le Floch O. and Chajes V. (2002): N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France. Int. J. Cancer, 98, 78-83.
61. Mattick J. S., Nickless J., Mizugaki M., Yang C. Y., Uchiyama S. and Wakil S. J. (1983): The architecture of the animal fatty acid synthetase. I. Proteolytic dissection and peptide mapping. J. Biol. Chem., 258, 15300-15304.
62. Menendez J. A., Colomer R., Cortes-Funes H. and Lupu R. (2004): Tumor-associated fatty acid synthase hyperactivity regulates breast cancer cell sensitivity to paclitaxel (Taxol)-induced apoptosis. Proc. Am. Assoc. Cancer Res., 45, LB-283.
63. Menendez J. A., Colomer R. and Lupu R. (2004): Inhibition of tumor-associated fatty acid synthase activity enhances vinorelbine (Navelbine®)-induced cytotoxicity and apoptotic cell death in human breast cancer cells. Oncol. Rep., 12, 411-422.
64. Menendez J. A., Lupu R. and Colomer R. (2004): 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., 84, 183-195.
65. Menendez J. A., Mehmi I., Atlas E., Colomer R. and Lupu R. (2004): Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-κB. Int. J. Oncol., 24, 591-608.
66. Menendez J. A., Ropero S., Mehmi I., Atlas E., Colomer R. and Lupu R. (2004): Overexpression and hyperactivity of breast cancer-associated fatty acid synthase (oneogenic antigen-519) is insensitive to normal arachidonic fatty acid-induced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal α-linolenic and γ-linolenic fatty acids: a novel mechanism by which dietary fat can alter mammary tumorigenesis. Int J Oncol., 24, 1369-1383.
67. Menendez J. A., Vellon L., Mehmi I., Oza B. P., Ropero S., Colomer R. and Lupu R. (2004): Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells. Proc. Natl. Acad. Sci. USA, 101, 10715-10720.
68. Menendez J., Oza B. P., Atlas E., Vazquez-Martin A., Colomer R. and Lupu R. (2004): The anorectic fatty acid synthase (FAS) inhibitor C75 regulates genomic and non-genomic estrogen receptor-α activities in breast cancer cells. Proc. Am. Assoc. Cancer Res., 45, LB-269.
69. Menendez J. A., Oza B. P., Atlas E., Verma V. A., Mehmi I. and Lupu R. (2004): Inhibition of tumor-associated fatty acid synthase activity antagonizes estradiol- and tamoxifen-induced agonist transactivation of estrogen receptor (ER) in human endometrial adenocarcinoma cells. Oncogene, 23, 4945-4958.
70. Milgraum L. Z., Witters L. A., Pasternack G. R. and Kuhajda F. P. (1997): Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin. Cancer Res., 3, 2115-2120.
71. Moche M., Schneider G., Edwards P., Dehesh K. and Lindqvist Y. (1999): Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl carrier protein synthase. J. Biol. Chem., 274, 6031-6034.
72. Nemoto T., Terashima S., Kogure M., Hoshino Y., Kusakabe T., Suzuki T. and Gotoh M. (2001): Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia. Pathobiology, 69, 297-303.
73. Omura S. (1976): The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol. Rev., 40, 681-697.
74. Oshi A. K., Witkowski A. and Smith S. (1997): Mapping of functional interactions between domains of the animal fatty acid synthase by mutant complementation in vitro. Biochemistry, 36, 2316-2322.
75. Piyathilake C. J., Frost A. R., Manne U., Bell W. C., Weiss H., Heimburger D. C. and Grizzle W. E. (2000): The expression of fatty acid synthase (FAS) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum. Pathol., 31, 1068-1073.
76. Pizer E. S., Chrest F. J., DiGiuseppe J. A. and Han W. F. (1998): Pharmacological inhibition of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res., 58, 4611-4615.
77. Pizer E. S., Jackisch C., Wood F. D., Pasternack G. R., Davidson N. E. and Kuhajda F. P. (1996): Inhibition of fatty acid synthase induces programmed cell death in human breast cancer cells. Cancer Res., 56, 2745-2747.
78. Pizer E. S., Kurman R. J., Pasternack G. R. and Kuhajda F. P. (1997): Expression of fatty acid synthase is closely linked to proliferation and stromal decidualization in cycling endometrium. Int. J. Gynecol. Pathol., 16, 45-51.
79. Pizer E. S., Lax S. F., Kuhajda F. P., Pasternack G. R. and Kurman R. J (1998): Fatty acid synthase expression in endometrial carcinoma: correlation with cell proliferation and hormone receptors. Cancer, 83, 528-537.
80. Pizer E. S., Thupari J., Han W. F., Pinn M. L., Chrest F. J., Frehywot G. L., Townsend C. A. and Kuhajda F. P. (2000): Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res., 60, 213-218.
81. Pizer E. S., Wood F. D., Heine H. S., Romantsev F. E., Pasternack G. R. and Kuhajda F. P. (1996): Inhibition of fatty acid synthase delays disease progression in a xenograft model of ovarian cancer. Cancer Res., 56, 1189-1193.
82. Pizer E. S., Wood F. D., Pasternack G. R. and Kuhajda F. P. (1996): Fatty acid synthase (FAS): a target for cytotoxic antimetabolites in HL60 promyelocytic leukemia cells. Cancer Res., 56, 745-751.
83. Rangan V. S., Joshi A. K. and Smith S. (2001): Mapping the functional topology of the animal fatty acid synthase by mutant complementation in vitro. Biochem., 40, 10792-10799.
84. Rashid A., Pizer ES, Moga M., Milgraum LZ, Zahurak M, Pasternack GR, Kuhajda FP and Hamilton S. R. (1997): Elevation of fatty acid synthase expression and fatty acid synthetic activity in coloreclal neoplasia. Am. J. Pathol., 150, 201-208.
85. Roncari D. A. K. (1974): Mammalian fatty acid synthase. I. Purification and properties of human liver complex. Can. J. Biochem., 52, 221-230.
86. Ross J. S. and Fletcher J. A. (1998): The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells, 16, 413-428.
87. Shimano H., Yahagi N., Amemiya-Kudo M., Hasty A. H., Osuga J., Tamura Y., Shionoiri F., Iizuka Y., Ohashi K., Harada K., Gotoda T., Ishibashi S. and Yamada N. (1999): Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J. Biol. Chem., 274, 35832-35839.
88. Shurbaji M. S., Kuhajda F. P., Pasternack G. R. and Thurmond T. S. (1992): Expression of oncogenic antigen 519 (OA-519) in prostate cancer is a potential prognostic indicator. Am. J. Clin. Pathol., 97, 686-691.
89. Slamon D. J., Clark G. M., Wong S. J., Levin W. J., Ullrich A. and McGuire W. L. (1987): Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 235, 177-182.
90. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J. and Ullrich A. (1989): Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 244, 707-712.
91. Slamon D. J., Leyland-Jones B., Shak S., Fuchs H., Paton V., Bajamonde A., Fleming T., Eiermann W., Wolter J., Pegram M., Baselga J. and Norton L. (2001): Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med., 344, 783-779.
92. Sul H. S. and Wang D. (1998): Nutritional and hormonal regulation of enzymes in fat synthesis: studies of fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription. Annu. Rev. Nutr., 18, 331-351.
93. Swinnen J. V., Esquenet M., Goossens K., Heyns W. and Verhoeven G. (1997): Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP. Cancer Res., 57, 1086-1090.
94. Swinnen J. V., Heemers H., Deboel L., Foufelle F., Heyns W. and Verhoeven G. (2000): Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway. Oncogene, 19, 5173-5181.
95. Swinnen J. V., Roskams T., Joniau S., Poppel H. V., Oyen R., Baert L., Heyns W. and Verhoeven G. (2002): Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int. J. Cancer, 98, 19-22.
96. Swinnen J. V., Ulrix W., Heyns W. and Verhoeven G. (1997): Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins. Proc. Natl. Acad. Sci. USA, 94, 12975-12980.
97. Swinnen J. V., Vanderhoydonc F., Elgamal A. A., Eelen M., Vercaeren I., Joniau S., Van Poppel H., Baert L., Goossens K., Heyns W. and Verhoeven G. (2000): Selective activation of the fatty acid synthesis pathway in human prostate cancer. Int. J. Cancer., 88, 176-179.
98. Takahiro T., Shinichi K. and Toshimitsu S. (2003): Expression of fatty acid synthase as a prognostic indicator in soft tissue sarcomas. Clin. Cancer Res., 9, 2204-2212.
99. Thompson, B. J. and Smith S. (1985): Biosynthesis of fatty acids by lactating human breast epithelial cells: an evaluation of the contribution of the overall composition of human milk fat. Pediatr. Res., 19, 139-143.
100. Tsukamoto Y., Wong H., Mattick J. S. and Wakil S. J. (1983): The architecture of the animal fatty acid synthetase complex. IV. Mapping of active centers and model for the mechanism of action. J. Biol. Chem., 258, 15312-15322.
101. Vance D., Goldberg I., Mitsuhashi O. and Bloch K. (1972): Inhibition of fatty acid synthethases by the antibiotic cerulenin. Biochem. Biophys. Res. Commun., 48, 549-565.
102. Van de Sande T., De Schrijver E., Heyns W., Verhoeven G. and Swinnen J. V. (2002): Role of the phosphatidylinositol 3′--kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Res., 62, 642-646.
103. Vazquez-Martin A., Menendez J. A., Ropero S., Montero S., Cortes-Funes H. and Colomer R. (2002): Anthracycline resistance on breast cancer cells is reversed by inhibition of fatty acid synthase. Proc. Am. Assoc. Cancer Res., 43, #4709, 951.
104. Visca P., Alo P. L., Del Nonno F., Bottie C., Trombetta G., Marandino F., Filippi S., Di Tondo U. and Donnorso R. P. (1999): Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent non--neoplastic mucosa. Clin. Cancer Res., 5, 4111-4118.
105. Visca P., Sebastiani V., Pizer E. S., Botti C., De Carli P., Filippi S., Monaco S. and Alo P. L. (2003): Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma. Anticancer Res., 23, 335-339.
106. Vogel C. L., Cobleigh M. A., Tripathy D., Gutheil J. C., Harris L. N., Fehrenbacher L., Slamon D. J., Murphy M., Novotny W. F., Burchmore M., Shak S., Stewart S. J. and Press M. (2002): Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol., 20, 719-726.
107. Wakil S. (1989): Fatty acid synthase, a proficient multifunctional enzyme. Biochem. J., 28, 4523-4530.
108. Wang D. and Sul H. S. (1998): 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., 273, 25420-25426.
109. Wang S. C. and Hung M. C. (2000): Transcriptional targeting of the HER-2/neu oncogene. Drugs Today, 36, 835-843.
110. Warburg O. (1956): On the origin of cancer cells. Science, 123, 309-314.
111. Weiss L., Hoffmann G. E., Schreiber R., Andres H., Fuchs E., Korber E. and Kolb H. J. (1986): Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Biol. Chem., 367, 905-912.
112. Witkowski A., Rangan V. S., Randhawa Z. I., Amy C. M. and Smith S. (1991): Structural organization of the multifunctional animal fatty acid synthase. Int. J. Biochem., 198, 571-579.
113. Xing X., Wang S. C., Xia W., Zou Y., Shao R., Kwong K. Y., Yu Z., Zhang S., Miller S., Huang L. and Hung M. C. (2000): The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis. Nat. Med., 6, 189-195.
114. Xu Z-X., Stenzel W., Sasic S. M., Smart D. A. and Rooney S. A. (1993): Glucocorticoid regulation of fatty acid synthase gene-expression in fetal rat lung. Am. J. Physiol. 265, L140-L147.
115. Yakes FM, Chinratanalah W, Ritter CA, King W, Seelig S and Arteaga C. L. (2002): Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27. cyclin D1, and antitumor action. Cancer Res., 62, 4132-4141.
116. Yang Y. A., Han W. F., Morin P. J., Chrest F. J. and Pizer E. S. (2002): Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp. Cell Res., 279, 80-90.
117. Yang Y. A., Morin P. J., Han W. F., Chen T., Bornman D. M., Gabrielson E. W. and Pizer E. S. (2003): Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Exp. Cell Res., 282, 132-137.
118. Ye Q., Chung L. W., Li S. and Zhau H. E. (2000): Identification of a novel FAS/ER-α fusion transcript expressed in human cancer cells. Biochim. Biophys. Acta., 1493, 373-377.
119. Yu D. and Hung M-C. (2000): Role of erbB2 in breast cancer chemosensitivity. Bioessays, 22, 673-680.
120. Zhou W., Simpson P. J., McFadden J. M., Townsend C. A., Medghalchi S. M., Vadlamudi A., Finn M. L., Ronnett G. V. and Kuhajda F. P. (2003): Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res., 63. 7330-7337.