Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma

Molecular Cancer Therapeutics

Volumn 1, Issue 10, 2002, Pages 777-783

  Ng, Sylvia S W ^a,b   Tsao, Ming Sound ^a,b   Nicklee, Trudey ^b   Hedley, David W ^a,b  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AKT1 PROTEIN, HUMAN; ANDROSTANE DERIVATIVE; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; DRUG DERIVATIVE; ENZYME INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEMCITABINE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE; QUINAZOLINE DERIVATIVE; WORTMANNIN;

ADENOCARCINOMA; ANIMAL; APOPTOSIS; ARTICLE; CANCER TRANSPLANTATION; DRUG ANTAGONISM; FLUORESCENCE MICROSCOPY; FLUORESCENT ANTIBODY TECHNIQUE; HUMAN; IMAGE PROCESSING; IMMUNOHISTOCHEMISTRY; MALE; METABOLISM; MOUSE; MOUSE MUTANT; NICK END LABELING; PANCREAS TUMOR; PHOSPHORYLATION; SIGNAL TRANSDUCTION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADENOCARCINOMA; ANDROSTADIENES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; DEOXYCYTIDINE; ENZYME INHIBITORS; FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; IMMUNOHISTOCHEMISTRY; IN SITU NICK-END LABELING; MALE; MICE; MICE, SCID; MICROSCOPY, FLUORESCENCE; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MITOGEN-ACTIVATED PROTEIN KINASES; NEOPLASM TRANSPLANTATION; PANCREATIC NEOPLASMS; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 0036690404     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: None     Document Type: Article

References (19)

1. Matano, E., Tagliaferri, P., Libroia, A., Damiano, V., Fabbrocini, A., De Lorenzo, D., and Bianco, A. R. Gemcitabine combined with continuous infusion 5-fluorouracil in advanced and symptomatic pancreatic cancer: a clinical benefit-oriented phase II study. Br. J. Cancer, 82: 1772-1775, 2000. (Pubitemid 30307387)
2. Rosenberg, L. Treatment of pancreatic cancer. Int. J. Pancreatol., 22: 81-93, 1997.
3. Oikawa, T., Hitomi, J., Kono, A., Kaneko, E., and Yamaguchi, K. Frequent expression of genes of receptor tyrosine kinases and their ligands in human pancreatic cancer cells. Int. J. Pancreatol., 18: 15-23, 1995.
4. Korc, M., Chandrasekar, B., Yamanaks, Y., Friess, H., Buchuer, M., and Beger, H. G. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor α. J. Clin. Investig., 90: 1352-1360, 1992.
5. Yamanaka, Y., Friess, H., Kobrin, M. S., Buchler, M., Kunz, J., Beger, H. G., and Korc, M. Overexpression of Her2/neu oncogene in human pancreatic carcinoma. Hum. Pathol., 24: 1127-1134, 1993. (Pubitemid 23306246)
6. Moyer, J. D., Barbacci, E. G., Iwata, K. K., Arnold, L., Boman, B., Cunningham, A., DiOrio, C., Doty, J., Morin, M. J., Moyer, M. P., Neveu, M., Pollack, V. A., Pustilnik, L. R., Reynolds, M. M., Theleman, A., and Miller, P. Induction of apoptosis and cell cycle arrest by CP 384-774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res., 57: 4838-4848, 1997. (Pubitemid 27468992)
7. Crowder, R. J., and Freeman, R. S. Glycogen synthase kinase-3β activity is critical for neuronal death caused by inhibiting phosphatidylinositol kinase or Akt but not for death caused by nerve growth factor withdrawal. J. Biol. Chem., 275: 34266-34271, 2000.
8. Ng, S. S. W., Tsao, M. S., Nicklee, T., and Hedley, D. W. Wortmannin inhibits PKB/Akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin. Cancer Res., 7: 3269-3275, 2001. (Pubitemid 32963853)
9. Ng, S. S. W., Tsao, M. S., Chow, S., and Hedley, D. W. Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res., 60: 5451-5455, 2000.
10. Coffer, P. J., Jin, J., and Woodgett, J. R. Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol activation. Biochem. J., 335: 1-13, 1998. (Pubitemid 28477043)
11. Reyes, G., Villanueva, A., Garcia, C., Sancho, F. J., Piulats, J., Lluis, F., and Capella, G. Orthotopic xenografts of human pancreatic carcinomas acquire genetic aberrations during dissemination in nude mice. Cancer Res., 56: 5713-5719.
12. Scheid, M. P., and Duronio, V. Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/Akt: involvement of MEK upstream of Bad phosphorylation. Proc. Natl. Acad. Sci. USA, 95: 7439- 7444, 1998.
13. Graff, J. R., Konicek, B. W., McNulty, A. M., Wang, Z., Houck, K., Allen, S., Paul, J. D., Hbaiu, A., Goode, R. G., Sandusky, G. E., Vessella, R. L., and Neubauer, B. L. Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression. J. Biol. Chem., 275: 24500-24505, 2000. (Pubitemid 30626543)
14. Jones, R. G., Parsons, M., Bonnard, M., Chan, V. S., Yeh, W. C., Woodgett, J. R., and Ohashi, P. S. Protein kinase B regulates T lymphocyte survival, nuclear factor κB activation and Bcl-X(L) levels in vivo. J. Exp. Med., 191: 1721-1734, 2000.
15. Bruns, C. J., Solorzano, C. C., Harbison, M. T., Ozawa, S., Tsan, R., Fan, D., Abbruzzese, J., Traxler, P., Buchdunger, E., Radinsky, R., and Fidler, I. J. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic cancer carcinoma. Cancer Res., 60: 2926-2935, 2000. (Pubitemid 30395817)
16. Sirotnak, F. M., Zakowski, M. F., Miller, V. A., Scher, H. I., and Kris, M. G. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD-1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin. Cancer Res., 6: 4885- 4892, 2000.
17. Frassoldati, A., Adami, F., Banzi, C., Criscuolo, M., Piccinini, L., and Silingardi, V. Changes of biological features in breast cancer cells determined by primary chemotherapy. Breast Cancer Res. Treat., 44: 185-192, 1997. (Pubitemid 27296377)
18. Baselga, J., Norton, L., Albanell, J., Kim, Y. M., and Mendelsohn, J. Recombinant humanized anti-Her2 antibody (HerceptinTM) enhances the antitumor activity of paclitaxel and doxorubicin against Her2/neu overexpressing human breast cancer xenografts. Cancer Res., 58: 2825-2831, 1998. (Pubitemid 28311914)
19. Downward, J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opinion Cell. Biol., 10: 262-267, 1998. (Pubitemid 28174769)