The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1α and vascular endothelial growth factor formation

Molecular Cancer Therapeutics

Volumn 2, Issue 3, 2003, Pages 235-243

  Welsh, Sarah J ^a   Williams, Ryan R ^a   Birmingham, Anne ^a   Newman, David J ^b   Kirkpatrick, D Lynn ^c   Powis, Garth ^a  

^a UNIVERSITY OF ARIZONA   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c Biomira Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DISULFIDE; FUSED HETEROCYCLIC RINGS; HIF1A PROTEIN, HUMAN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMIDAZOLE DERIVATIVE; INDUCIBLE NITRIC OXIDE SYNTHASE; IV 2 COMPOUND; LUCIFERASE; MEMBRANE PROTEIN; NITRIC OXIDE SYNTHASE; NOS2 PROTEIN, MOUSE; NOS2A PROTEIN, HUMAN; PLEUROTIN; THIOREDOXIN; TRANSCRIPTION FACTOR; TXNDC2 PROTEIN, MOUSE; VASCULOTROPIN A;

ANIMAL; ARTICLE; BREAST TUMOR; CELL CULTURE; CELL DIVISION; COLON TUMOR; DOWN REGULATION; DRUG ANTAGONISM; DRUG EFFECT; ENZYME IMMUNOASSAY; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; KIDNEY TUMOR; METABOLISM; MOUSE; MOUSE MUTANT; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL DIVISION; COLONIC NEOPLASMS; DISULFIDES; DOWN-REGULATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IMIDAZOLES; IMMUNOENZYME TECHNIQUES; KIDNEY NEOPLASMS; LUCIFERASES; MEMBRANE PROTEINS; MICE; MICE, SCID; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE II; THIOREDOXIN; TRANSCRIPTION FACTORS; TUMOR CELLS, CULTURED; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 0142144338     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: None     Document Type: Article

References (74)

1. Semenza, G. L. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit. Rev. Biochem. Mol. Biol., 35: 71-103, 2000. (Pubitemid 30253678)
2. Semenza, G. L. HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol. Med., 8 (Suppl. 4): 62-67, 2002.
3. Semenza, G. L. Involvement of hypoxia-inducible factor 1 in human cancer. Intern. Med., 41: 79-83, 2002. (Pubitemid 34223708)
4. 2 tension. Proc. Natl. Acad. Sci. USA, 92: 5510-5514, 1995.
5. Kallio, P., Okamoto, K., O'Brian, S., Carrero, P., Makino, Y., Tanaka, H., and Poellinger, L. Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor 1α. EMBO J., 17: 6573-6586, 1998. (Pubitemid 28521792)
6. Ema, M., Hirota, K., Mimura, J., Abe, H., Yodoi, J., Sogawa, K., Poellinger, L., and Fujii-Kuriyama, Y. Molecular mechanisms of transcription activation by HLF and HIF-1α in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J., 18: 1905-1914, 1999. (Pubitemid 29158534)
7. Carrero, P., Okamoto, K., Coumailleau, P., O'Brien, S., Tanaka, H., and Poellinger, L. Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1α. Mol. Cell. Biol., 20: 402-415, 2000. (Pubitemid 30002581)
8. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., and Whitelaw, M. L. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science (Wash. DC), 295: 858-861, 2002. (Pubitemid 34118367)
9. Jiang, B., Agani, F., Passaniti, A., and Semenza, G. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res., 57: 5328-5335, 1997. (Pubitemid 27516371)
10. Minchenko, A., Salceda, S., and Bauer, T. Hypoxia regulatory elements of the human vascular endothelial growth factor gene. Cell Mol. Biol. Res., 40: 35-39, 1994. (Pubitemid 24292725)
11. Huang, L., Gu, J., Schau, M., and Bunn, H. Regulation of hypoxiainducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteosome pathway. Proc. Natl. Acad. Sci. USA, 95: 7987-7992, 1998.
12. Kallio, P. J., Wilson, W. J., O'Brien, S., Makino, Y., and Poellinger, L. Regulation of the hypoxia-inducible factor-1α by the ubiquitin-proteosome pathway. J. Biol. Chem., 274: 6519-6525, 1999. (Pubitemid 29111068)
13. Semenza, G. L. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell, 107: 43-54, 2001.
14. Wenger, R., and Gassmann, M. Oxygen and the hypoxia-inducible factor 1. Eur. J. Biochem., 246: 155-165, 1997.
15. An, W., Kanekal, M., Simon, M., Maltepe, E., Blagosklonny, M., and Neckers, L. Stabilization of wild-type p53 by hypoxia-inducible factor 1α. Nature (Lond.), 392: 405-408, 1998.
16. Ravi, R., Mookerjee, B., Bhujwalla, Z., Sutter, C., Artemov, D., Zeng, Q., Dillehay, L., Madan, A., Semenza, G., and Bedi, A. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α. Genes Dev., 14: 34-44, 2000. (Pubitemid 30051577)
17. Jiang, B., Jiang, G., Zheng, J., Lu, Z., Hunter, T., and Vogt, P. Phosphatidylinositol 3-kinase signaling controls the levels of hypoxiainducible factor-1. Cell Growth Differ., 12: 363-369, 2001. (Pubitemid 32685637)
18. Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., Stokoe, D., and Giaccia, A. J. Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev., 14: 391-396, 2000. (Pubitemid 30131884)
19. Isaacs, J. S., Jung, Y. J., Mimnaugh, E. G., Martinez, A., Cuttitta, F., and Neckers, L. M. Hsp90 regulates a VHL-independent HIF-1a degradative pathway. J. Biol. Chem., 277: 29936-29944, 2002.
20. Chandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., and Schumacker, P. T. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxiainducible factor-1α during hypoxia: a mechanism of O2 sensing. J. Biol. Chem., 275: 25130-25138, 2000.
21. Haddad, J. J., and Land, S. C. A non-hypoxic ROS sensitive pathway mediates TNF-α-dependent regulation of HIF-1α. FEBS Lett., 505: 269-274, 2001.
22. Huang, L. E., Arany, Z., and Livingston, D. M. Activation of hypoxia inducible transcription factor depends primarily upon redox-sensitive stabilization of its α subunit. J. Biol. Chem., 271: 32253-32259, 1996. (Pubitemid 26422262)
23. Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., and Schumaker, P. T. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA, 95: 11715-11720, 1998. (Pubitemid 28460480)
24. Salceda, S., and Caro, J. Hypoxia-inducible factor 1α (HIF-1α) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions: its stabilization by hypoxia depends upon redox-induced changes. J. Biol. Chem., 272: 22642-22647, 1997. (Pubitemid 27386079)
25. Beasley, N. J., Leek, R., Alam, M., Turley, H., Cox, G. J., Gatter, K., Millard, P., Fuggle, S., and Harris, A. L. Hypoxia-inducible factors HIF-1α and HIF-2α in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res., 62: 2493-2497, 2002. (Pubitemid 34462724)
26. Haugland, H. K., Vukovic, V., Pintilie, M., Fyles, A. W., Milosevic, M., Hill, R. P., and Hedley, D. W. Expression of hypoxia-inducible factor-1α in cervical carcinomas: correlation with tumor oxygenation. Int. J. Radiat. Oncol. Biol. Phys., 53: 854-861, 2002. (Pubitemid 34722629)
27. Koukourakis, M. I., Giatromanolaki, A., Sividris, E., Simopoulos, C., Turley, H., Talks, K., Gatter, K. C., and Harris, A. L. Hypoxia-inducible factor (HIF1α and HIF2α), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys., 53: 1192-1202, 2002. (Pubitemid 34787855)
28. Nakayama, K., Kanzaki, A., Hata, K., Katabuchi, H., Okamura, H., Miyazaki, K., Fukumoto, M., and Takebayashi, Y. Hypoxia-inducible factor 1 alpha (HIF-1α) gene expression in human ovarian carcinoma. Cancer Lett., 176: 215-223, 2002. (Pubitemid 34136021)
29. Schindl, M., Schoppmann, S. F., Samonigg, H., Hausmaninger, H., Kwasny, W., Gnant, M., Jakesz, R., Kubista, E., Birner, P., and Oberhuber, G. Overexpression of hypoxia-inducible factor 1α is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin. Cancer Res., 8: 1831-1837, 2002. (Pubitemid 34633742)
30. Sondergaard, K. L., Hilton, D. A., Penney, M., Ollerenshaw, M., and Demaine, A. G. Expression of hypoxia-inducible factor 1α in tumours of patients with glioblastomas. Neuropathol. Appl. Neurobiol., 28: 210-217, 2002. (Pubitemid 34639443)
31. Turner, K. J., Moore, J. W., Jones, A., Taylor, C. F., Cuthbert-Heavens, D., Han, C., Leek, R. D., Gatter, K. C., Maxwell, P. H., Ratcliffe, P. J., Cranston, D., and Harris, A. L. Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res., 62: 2957-2961, 2002. (Pubitemid 34525785)
32. Clifford, S. C., Cockman, M. E., Smallwood, A. C., Mole, D. R., Woodward, E. R., Maxwell, P. H., Ratcliffe, P. J., and Maher, E. R. Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. Hum. Mol. Genet., 10: 1029-1038, 2001. (Pubitemid 32447780)
33. Wiesener, M. S., Munchenhagen, P. M., Berger, I., Morgan, N. V., Roigas, J., Jurgensen, J. S., Gruber, G., Maxwell, P. H., Loning, S. A., Frei, U., Maher, E. R., Grone, H. J., and Eckardt, K. U. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1α in clear cell renal carcinomas. Cancer Res., 61: 5215-5222, 2001. (Pubitemid 32681556)
34. Krieg, M., Haas, R., Brauch, H., Acker, T., Flamme, I., and Plate, K. H. Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene, 19: 5435-5443, 2000. (Pubitemid 32000910)
35. Maxwell, P. H., Weisener, M. S., Chang, G. W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., and Ratcliffe, P. J. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature (Lond.), 399: 271-275, 1999. (Pubitemid 29246458)
36. Schoenfeld, A. R., Parris, T., Eisenberger, A., Davidowitz, E. J., De Leon, M., Talasazan, F., Devarajan, P., and Burk, R. D. The von Hippel-Lindau tumor suppressor gene product protects cells from UV-mediated apoptosis. Oncogene, 19: 5851-5857, 2000. (Pubitemid 32005365)
37. Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., and Kaelin, W. G., Jr. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell, 1: 237-246, 2002. (Pubitemid 41039148)
38. Harris, A. L. Hypoxia: a key regulatory factor in tumour growth. Nat. Rev. Cancer, 2: 38-47, 2002. (Pubitemid 37328806)
39. Powis, G., Mustacich, D., and Coon, A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radic. Biol. Med., 29: 312-322, 2000.
40. Powis, G., and Montfort, W. R. Properties and biological activities of thioredoxins. Annu. Rev. Pharmacol. Toxicol., 41: 261-295, 2001. (Pubitemid 32385890)
41. Mustacich, D., and Powis, G. Thioredoxin reductase. Biochem. J., 346: 1-8, 2000. (Pubitemid 30113812)
42. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., and Ichijo, H. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO Journal, 17: 2596-2606, 1998. (Pubitemid 28221195)
43. Watson, J. A., Rumsby, M. G., and Wolowacz, R. G. Phage display identifies thioredoxin and superoxide dismutase as novel protein kinase C-interacting proteins: thioredoxin inhibits protein kinase C-mediated phosphorylation of histones. Biochem. J., 343: 301-305, 1999. (Pubitemid 29511760)
44. Hayashi, T., Ueno, Y., and Okamoto, T. Oxidoreductive regulation of nuclear factor κB: involvement of a cellular reducing catalyst thioredoxin. J. Biol. Chem., 268: 11380-11388, 1993. (Pubitemid 23162336)
45. Makino, Y., Yoshikawa, N., Okamoto, K., Hirota, K., Yodoi, J., Makino, I., and Tanaka, H. Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function. J. Biol. Chem., 274: 3182-3188, 1999. (Pubitemid 29075407)
46. Ueno, M., Masutani, H., Jun Arai, R., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J., and Nikaido, T. Thioredoxindependent redox regulation of p53-mediated p21 activation. J. Biol. Chem., 274: 35809-35815, 2000.
47. Baker, A., Payne, C. M., Briehl, M. M., and Powis, G. Thioredoxin, a gene found overexpressed in human cancer, inhibits apoptosis in vitro and in vivo. Cancer Res., 57: 5162-5167, 1997. (Pubitemid 27498136)
48. Gallegos, A., Gasdaska, J. R., Taylor, C. W., Paine-Murrieta, G. D., Goodman, D., Gasdaska, P. Y., Berggren, M., Briehl, M. M., and Powis, G. Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of breast cancer cells. Cancer Res., 56: 5765-5770, 1996. (Pubitemid 26422186)
49. Freemerman, A. J., and Powis, G. A redox-inactive thioredoxin reduces growth and enhances apoptosis in WEHI7.2 cells. Biochem. Biophys. Res. Commun., 274: 136-141, 2000. (Pubitemid 30496769)
50. Gasdaska, P. Y., Oblong, J. E., Cotgreave, I. A., and Powis, G. The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived factor (ADF): thioredoxin mRNA is elevated in some human tumors. Biochim. Biophys. Acta, 1218: 292-296, 1994. (Pubitemid 24252524)
51. Berggren, M., Gallegos, A., Gasdaska, J. R., Gasdaska, P. Y., Warneke, J., and Powis, G. Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res., 16: 3459-3466, 1996. (Pubitemid 27084998)
52. Nakamura, H., Bai, J., Nishinaka, Y., Ueda, S., Sasada, T., Ohshio, G., Imamura, M., Takabayashi, A., Yamaoka, Y., and Yodoi, J. Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer. Cancer Detect. Prevent., 24: 53-60, 2000. (Pubitemid 30152740)
53. Grogan, T. M., Fenoglio-Prieser, C., Zeheb, R., Bellamy, W., Frutiger, Y., Vela, E., Stemmerman, G., MacDonald, J., Richter, L., Gallegos, A., and Powis, G. Thioredoxin, a puntative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival. Hum. Pathol., 31: 475-481, 2000. (Pubitemid 30262870)
54. Gallegos, A., Raffel, J., Bhattacharyya, A. K., and Powis, G. Increased expression of thioredoxin in human primary and metastatic colon cancer. Proc. Am. Assoc. Cancer Res., 41: 189, 2000.
55. Kakolyris, S., Giatromanolaki, A., Koukourakis, M., Powis, G., Souglakos, J., Sivridis, E., Georgoulias, V., Gatter, K. C., and Harris, A. L. Thioredoxin expression is associated with lymph node status and prognosis in early operable non small cell lung cancer. Clin. Cancer Res, 7: 3087-3091, 2001. (Pubitemid 32963828)
56. Welsh, S. J., Bellamy, W. T., Briehl, M., and Powis, G. The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor-1α protein expression: Trx-1 over-expression results in increased vascular endothelial growth factor production and enhanced angiogenesis. Cancer Res., 62: 5089-5095, 2002. (Pubitemid 34984438)
57. Powis, G., Kirkpatrick, D. L., Angulo, M., and Baker, A. Thioredoxin redox control of cell growth and death and the effects of inhibitors. Chem. Biol. Interact., 111-112: 23-24, 1998.
58. Wipf, P., Hopkins, T. D., Jung, J-K., Rodriguez, S., Birmingham, A., Southwick, E. C., Lazo, J. S., and Powis, G. New inhibitors of the thioredoxin-thioredoxin reductase system based on a napthoquinone spiroketal natural product lead. Bioorg. Med. Chem. Lett., 11: 2637-2641, 2001. (Pubitemid 32823373)
59. Kirkpatrick, D. L., Watson, S., Kunkel, M., Fletcher, S., Ulhaq, S., and Powis, G. Parallel syntheses of disulfide inhibitors of the thioredoxin redox system as potential antitumor agents. Anticancer Drug Des., 14: 421-432, 1999. (Pubitemid 30168574)
60. Kirkpatrick, D. L., Kuperus, M., Dowdeswell, M., Potier, N., Donald, L. J., Kunkel, M., Berggen, M., Angulo, M., and Powis, G. Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2-imidazolyl disulfides. Biochem. Pharmacol., 55: 987-994, 1998. (Pubitemid 28167720)
61. Kunkel, M. W., Kirkpatrick, D. L., Johnson, J. I., and Powis, G. Cell line-directed screening assay for inhibitors of thioredoxin reductase signaling as potential anti-cancer drugs. Anticancer Drug Des., 12: 659-670, 1997. (Pubitemid 28004682)
62. Park, J. G., Kramer, B. S., Steinberg, S. M., Carmichel, J., Collins, J. M., Minna, J. D., and Gazdar, A. F. Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. Cancer Res., 47: 5875-5879, 1987. (Pubitemid 18018721)
63. Flaherty, D. M., Monick, M. M., and Hunninghake, G. W. AP endonucleases and the many functions of Ref-1. Am. J. Respir. Cell Mol. Biol., 25: 6447-6449, 2001.
64. Hirota, K., Matsui, M., Iwata, S., Nishiyama, A., Mori, K., and Yodoi, J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc. Natl. Acad. Sci. USA, 94: 3633-3638, 1997. (Pubitemid 27180424)
65. Hirota, K., and Semenza, G. J. Rac1 activity is required for the activation of hypoxia-inducible factor 1. J. Biol. Chem., 276: 21166-21172, 2001.
66. Lee, S. R., Yang, K. S., Kwon, J., Lee, C., Jeong, W., and Rhee, S. G. Reversible inactivation of the tumor suppressor PTEN by H2O2. J. Biol. Chem., 277: 20336-20342, 2002. (Pubitemid 34967328)
67. Neufeld, G., Kessler, O., Vadasz, Z., and Gluzman-Poltorak, Z. The contribution of proangiogenic factors to the progression of malignant disease: role of vascular endothelial growth factor and its receptors. Surg. Oncol. Clin. N. Am., 10: 339-356, 2001. (Pubitemid 32472534)
68. Bellamy, W., Richter, L., Sirjani, D., Roxas, C., Glinsmann-Gibson, B., Frutiger, Y., Grogan, T., and List, A. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood, 97: 1427-1434, 2000. (Pubitemid 32183769)
69. Claffey, K. P., Brown, L. F., and Del Aguila, L. F. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis and experimental metastasis. Cancer Res., 56: 172-181, 1996. (Pubitemid 26010397)
70. Kim, K. J., Li, B., and Winer, J. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature (Lond.), 362: 841-844, 1993. (Pubitemid 23132159)
71. Millauer, B., Shawer, L. K., and Plate, K. H. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature (Lond.), 367: 576-579, 1994.
72. Liu, Y., Cox, S. R., Morita, T., and Kourembanas, S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ. Res., 77: 638-643, 1995.
73. Forsythe, J. A., Jiang, B. H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., and Semenza, G. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor-1. Mol. Cell. Biol., 16: 4604-4613, 1996. (Pubitemid 26272112)
74. Xiong, S., Grijalva, R., Zhang, L., Ngeugen, N., Pisters, P., Pollock, R., and Yu, D. Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-β1-activated p38 signaling pathway enhances endothelial cell migration. Cancer Res., 61: 1727-1732, 2001. (Pubitemid 34292611)