Potential of ErbB4 antibodies for cancer therapy

Future Oncology

Volumn 6, Issue 1, 2010, Pages 37-53

  Hollmén, Maija ^a   Elenius, Klaus ^b  

^a UNIVERSITY OF TURKU   (Finland)

^b TURKU UNIVERSITY HOSPITAL   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; HUMAX; MATUZUMAB; MONOCLONAL ANTIBODY; NEU DIFFERENTIATION FACTOR; NIMOTUZUMAB; PANITUMUMAB; PERTUZUMAB; STAT5 PROTEIN; TRASTUZUMAB; UNCLASSIFIED DRUG; ZALUTUMUMAB;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; BINDING SITE; BIOLOGICAL ACTIVITY; BLADDER CARCINOMA; BREAST CANCER; CANCER THERAPY; CLINICAL TRIAL; COLORECTAL CANCER; COLORECTAL CARCINOMA; CONFORMATIONAL TRANSITION; DIMERIZATION; DOWN REGULATION; ENDOMETRIUM CARCINOMA; EPENDYMOMA; GENE MUTATION; GLIOBLASTOMA; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG CANCER; LUNG CARCINOMA; LUNG NON SMALL CELL CANCER; MENINGIOMA; OVARY CANCER; OVARY CARCINOMA; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROSTATE CARCINOMA; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; PROTEIN TARGETING; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SARCOMA; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; THYROID CARCINOMA;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 75149192831     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.09.144     Document Type: Review

References (145)

1. Linggi B, Carpenter G: ErbB receptors: new insights on mechanisms and biology. Trends Cell Biol. 16(12), 649-656 (2006).
2. Wieduwilt M, Moasser M: The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell. Mol. Life Sci. 65(10), 1566-1584 (2008).
3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785), 177-182 (1987). ■ First demonstration of the significance of ErbB2 amplification for breast cancer disease outcome.
4. Linardou H, Dahabreh I, Bafaloukos D, Kosmidis P, Murray S: Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat. Rev. Clin. Oncol. 6(6), 352-366 (2009).
5. Hynes NE, Lane HA: ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer 5(5), 341-354 (2005).
6. Gullick WJ: c-erbB-4/HER4: friend or foe? J. Pathol. 200(3), 279-281 (2003).
7. Muraoka-Cook RS, Sandahl M, Husted C et al.: The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Mol. Biol. Cell 17(9), 4118-4129 (2006).
8. Jones F, Welte T, Fu X, Stern D: ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J. Cell. Biol. 147(1), 77-88 (1999).
9. Muraoka-Cook R, Feng S, Strunk K, Earp HR: ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition. J. Mammary Gland Biol. Neoplasia 13(2), 235-246 (2008).
10. Sundvall M, Iljin K, Kilpinen S, Sara H, Kallioniemi O, Elenius K: Role of ErbB4 in breast cancer. J. Mammary Gland Biol. Neoplasia 13(2), 259-268 (2008).
11. Junttila TT, Sundvall M, Lundin M et al.: Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells. Cancer Res. 65(4), 1384-1393 (2005). ■ Demonstrates the importance of ErbB4 cleavage in estrogen-regulated growth of breast cancer.
12. Zeng N, Liu L, McCabe M, Jones D, Ichimura K, Collins V: Real-time quantitative PCR ana lysis with FRET probes reveals differential expression of the four ERBB4 juxtamembrane-region variants between medulloblastoma and pilocytic astrocytoma. Neuropathol. Appl. Neurobiol. 35(4), 353-366 (2008).
13. Ljuslinder I, Malmer B, Isaksson-Mettävainio M et al.: ErbB 1-4 expression alterations in primary colorectal cancers and their corresponding metastases. Anticancer Res. 29(5), 1489-1494 (2009).
14. Rickman O, Vohra P, Sanyal B et al.: Analysis of ErbB receptors in pulmonary carcinoid tumors. Clin. Cancer Res. 15(10), 3315-3324 (2009).
15. Xu S, Kitayama J, Yamashita H, Souma D, Nagawa H: Nuclear translocation of HER-4/c-erbB-4 is significantly correlated with prognosis of esophageal squamous cell carcinoma. J. Surg. Oncol. 97(1), 44-50 (2008).
16. Hollmén M, Määttä J, Bald L, Sliwkowski M, Elenius K: Suppression of breast cancer cell growth by a monoclonal antibody targeting cleavable ErbB4 isoforms. Oncogene 28(10), 1309-1319 (2009). ■ Characterizes an ErbB4 JM-a specific monoclonal antibody that inhibits shedding of ErbB4 and has antitumor activity in vitro.
17. Prickett T, Agrawal N, Wei X et al.: Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat. Genet. 41(10), 1127-1132 (2009). ■ ■ Reveals the presence of activating ErbB4 mutations in metastatic melanoma. The findings provide strong evidence for an oncogenic role of ErbB4 and for the rationale of targeting mutated ErbB4 in cancer.
18. Starr A, Greif J, Vexler A et al.: ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy. Int. J. Cancer 119(2), 269-274 (2006).
19. Tang CK, Concepcion XZ, Milan M, Gong X, Montgomery E, Lippman ME: Ribozyme-mediated down-regulation of ErbB-4 in estrogen receptor-positive breast cancer cells inhibits proliferation both in vitro and in vivo. Cancer Res. 59(20), 5315-5322 (1999). ■ Demonstration that specific ribozymemediated downregulation of ErbB4 results in decreased growth of breast cancer cells.
20. Kurppa K, Elenius K: Mutated ERBB4: a novel drug target in metastatic melanoma? Pigment Cell Melanoma Res. 22(6), 708-710 (2009).
21. Warren C, Landgraf R: Signaling through ERBB receptors: multiple layers of diversity and control. Cell Signal. 18(7), 923-933 (2006).
22. Burgess A, Cho H, Eigenbrot C et al.: An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol. Cell 12(3), 541-552 (2003).
23. Garrett T, McKern N, Lou M et al.: The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell 11(2), 495-505 (2003). ■ A structural demonstration of why ErbB2 does not bind any known ligand and is poised to interact with the other ErbB family members.
24. Graus-Porta D, Beerli RR, Daly JM, Hynes NE: ErbB2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 16, 1647-1655 (1997)
25. Guy P, Platko J, Cantley L, Cerione R, Carraway KR: Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc. Natl Acad. Sci. USA 91(17), 8132-8136 (1994).
26. Bleeker W, Lammerts van Bueren J, van Ojik H et al.: Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy. J. Immunol. 173(7), 4699-4707 (2004).
27. Crombet-Ramos T, Rak J, Pérez R, Viloria-Petit A: Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: a humanized anti-EGFR antibody. Int. J. Cancer 101(6), 567-575 (2002).
28. Li S, Schmitz K, Jeffrey P, Wiltzius J, Kussie P, Ferguson K: Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7(4), 301-311 (2005).
29. Schmiedel J, Blaukat A, Li S, Knöchel T, Ferguson K: Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization. Cancer Cell 13(4), 365-373 (2008).
30. Jakobovits A, Amado R, Yang X, Roskos L, Schwab G: From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nat. Biotechnol. 25(10), 1134-1143 (2007).
31. Lammerts van Bueren J, Bleeker W, Brännström A et al.: The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intraand intermolecular flexibility. Proc. Natl Acad. Sci. USA 105(16), 6109-6114 (2008).
32. Bastholt L, Specht L, Jensen K et al: Phase I/ II clinical and pharmacokinetic study evaluating a fully human monoclonal antibody against EGFr (HuMax-EGFr) in patients with advanced squamous cell carcinoma of the head and neck. Radiother. Oncol. 85(1), 24-28 (2007).
33. Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin. Ther. 30(1), 14-30 (2008).
34. Reuter C, Morgan M, Eckardt A: Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck. Br. J. Cancer 96(3), 408-416 (2007).
35. Carter P: Potent antibody therapeutics by design. Nat. Rev. Immunol. 6(5), 343-357 (2006).
36. Cohenuram M, Saif M: Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs 18(1), 7-15 (2007).
37. Ruuls S, Lammerts van Bueren J, van de Winkel J, Parren P: Novel human antibody therapeutics: the age of the Umabs. Biotechnol J. 3(9-10), 1157-1171 (2008).
38. Cho HS, Mason K, Ramyar KX et al.: Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421(6924), 756-760 (2003).
39. Junttila T, Akita R, Parsons K et al.: Ligandindependent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15(5), 429-440 (2009).
40. Liu P, Liu X, Li Y et al.: Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells. Cancer Biol. Ther. 5(6), 657-664 (2006).
41. Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J: Trastuzumab (Herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 61(12), 4744-4749 (2001).
42. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5(4), 317-328 (2004).
43. Schmitz K, Ferguson K: Interaction of antibodies with ErbB receptor extracellular regions. Exp. Cell Res. 315(4), 659-670 (2009).
44. Elenius K, Choi CJ, Paul S, Santiestevan E, Nishi E, Klagsbrun M: Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene 18(16), 2607-2615 (1999).
45. Sundvall M, Korhonen A, Paatero I et al.: Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms. Proc. Natl Acad. Sci. USA 105(11), 4162-4167 (2008).
46. Omerovic J, Santangelo L, Puggioni E et al.: The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation. FASEB J. 21(11), 2849-2862 (2007).
47. Zeng F, Xu J, Harris R: Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB J. 23(6), 1935-1945 (2009).
48. Feng S, Muraoka-Cook R, Hunter D et al.: The E3 ubiquitin ligase WWP1 selectively targets HER4 and its proteolytically derived signaling isoforms for degradation. Mol. Cell. Biol. 29(3), 892-906 (2009).
49. Kainulainen V, Sundvall M, Maatta JA, Santiestevan E, Klagsbrun M, Elenius K: A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J. Biol. Chem. 275(12), 8641-8649 (2000).
50. Muraoka-Cook R, Sandahl M, Strunk K et al.: ErbB4 splice variants Cyt1 and Cyt2 differ by sixteen amino acids and exert opposing effects on the mammary epithelium in vivo. Mol. Cell. Biol. 29(18), 4935-48 (2009). ■ ■ A demonstration of the differential functions of the ErbB4 isoforms for mammary tissue differentiation and proliferation in vivo.
51. Rio C, Buxbaum JD, Peschon JJ, Corfas G: Tumor necrosis factor-α-converting enzyme is required for cleavage of erbB4/HER4. J. Biol. Chem. 275(14), 10379-10387 (2000).
52. Elenius K, Corfas G, Paul S et al.: A novel juxtamembrane domain isoform of HER4/ ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J. Biol. Chem. 272(42), 26761-26768 (1997).
53. Cheng QC, Tikhomirov O, Zhou W, Carpenter G: Ectodomain cleavage of ErbB-4: characterization of the cleavage site and m80 fragment. J. Biol. Chem. 278(40), 38421-38427 (2003).
54. Lee HJ, Jung KM, Huang YZ et al.: Presenilin-dependent γ-secretase-like intramembrane cleavage of ErbB4. J. Biol. Chem. 277(8), 6318-6323 (2002). ■ ■ One of the first reports of a novel signaling mechanism of ErbB4 involving a two-step proteolytic release of a soluble intracellular domain of ErbB4 that translocates to the nucleus and regulates transcription.
55. Ni CY, Murphy MP, Golde TE, Carpenter G: γ -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294(5549), 2179-2181 (2001). ■ ■ One of the first reports of a novel signaling mechanism of ErbB4 involving a two-step proteolytic release of a soluble intracellular domain of ErbB4 that translocates to the nucleus and regulates transcription.
56. Heldin C, Ericsson J: Signal transduction. RIPping tyrosine kinase receptors apart. Science 294(5549), 2111-2113 (2001).
57. Williams C, Allison J, Vidal G et al.: The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J. Cell. Biol. 167(3), 469-478 (2004).
58. Komuro A, Nagai M, Navin NE, Sudol M: WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxylterminal fragment of ErbB-4 that translocates to the nucleus. J. Biol. Chem. 278(35), 33334-33341 (2003).
59. Linggi B, Carpenter G: ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional repression. J. Biol. Chem. 281(35), 25373-25380 (2006).
60. Zhu Y, Sullivan LL, Nair SS et al.: Coregulation of estrogen receptor by ERBB4/HER4 establishes a growthpromoting autocrine signal in breast tumor cells. Cancer Res. 66(16), 7991-7998 (2006).
61. Sardi S, Murtie J, Koirala S, Patten B, Corfas G: Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 127(1), 185-197 (2006). ■ ■ First demonstration of the in vivo significance of the novel nuclear signaling mechanism of ErbB4.
62. Määttä JA, Sundvall M, Junttila TT et al.: Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. Mol. Biol. Cell 17(1), 67-79 (2006). ■ A comparative ana lysis of the signaling properties of all the four ErbB4 isoforms.
63. Zeng F, Zhang M, Singh A, Zent R, Harris R: ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis. Mol. Biol. Cell 18(11), 4446-4456 (2007).
64. Naresh A, Long W, Vidal G et al.: The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res. 66(12), 6412-6420 (2006). ■ First characterization of a mechanism by which a BH3-like domain in ErbB4 promotes apoptosis.
65. Arasada R, Carpenter G: Secretase-dependent tyrosine phosphorylation of Mdm2 by the ErbB-4 intracellular domain fragment. J. Biol. Chem. 280(35), 30783-30787 (2005).
66. Srinivasan R, Poulsom R, Hurst HC, Gullick WJ: Expression of the c-erbB-4/ HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types. J. Pathol. 185(3), 236-245 (1998).
67. Abd El-Rehim D, Pinder S, Paish C et al.: Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. Br. J. Cancer 91(8), 1532-1542 (2004).
68. Bacus S, Chin D, Yarden Y, Zelnick C, Stern D: Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. Am. J. Pathol. 148(2), 549-558 (1996).
69. Barnes N, Khavari S, Boland G, Cramer A, Knox W, Bundred N: Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin. Cancer Res. 11(6), 2163-2168 (2005).
70. Haas S, Gevensleben H, Rabstein S et al.: Expression of heregulin, phosphorylated HER-2, HER-3 and HER-4 in HER-2 negative breast cancers. Oncol. Rep. 21(2), 299-304 (2009).
71. Kew T, Bell J, Pinder S et al.: c-erbB-4 protein expression in human breast cancer. Br. J. Cancer 82(6), 1163-1170 (2000).
72. Knowlden J, Gee J, Seery L et al.: c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 17(15), 1949-1957 (1998).
73. Koutras A, Kalogeras K, Dimopoulos M et al.: Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Br. J. Cancer 99(11), 1775-1785 (2008).
74. Sassen A, Rochon J, Wild P et al.: Cytogenetic ana lysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 10(1), R2 (2008).
75. Srinivasan R, Gillett CE, Barnes DM, Gullick WJ: Nuclear expression of the c-erbB-4/HER-4 growth factor receptor in invasive breast cancers. Cancer Res. 60(6), 1483-1487 (2000).
76. Suo Z, Risberg B, Kalsson MG et al.: EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival. J. Pathol. 196(1), 17-25 (2002).
77. Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM: Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J. Pathol. 200(3), 290-297 (2003).
78. Guler G, Iliopoulos D, Guler N, Himmetoglu C, Hayran M, Huebner K: Wwox and Ap2γ expression levels predict tamoxifen response. Clin. Cancer Res. 13(20), 6115-6121 (2007).
79. Naresh A, Thor A, Edgerton S, Torkko K, Kumar R, Jones F: The HER4/4ICD estrogen receptor coactivator and BH3-only protein is an effector of tamoxifen-induced apoptosis. Cancer Res. 68(15), 6387-6395 (2008).
80. Frogne T, Benjaminsen R, Sonne-Hansen K et al.: Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant. Breast Cancer Res. Treat. 114(2), 263-275 (2009).
81. Bièche I, Onody P, Tozlu S, Driouch K, Vidaud M, Lidereau R: Prognostic value of ERBB family mRNA expression in breast carcinomas. Int. J. Cancer 106(5), 758-765 (2003).
82. Lodge AJ, Anderson JJ, Gullick WJ, Haugk B, Leonard RC, Angus B: Type 1 growth factor receptor expression in node positive breast cancer: adverse prognostic significance of c-erbB-4. J. Clin. Pathol. 56(4), 300-304 (2003).
83. Wang S, Xiang B, Guix M et al.: Transforming growth factor β engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol. Cell. Biol. 28(18), 5605-5620 (2008).
84. Hamburger A: The role of ErbB3 and its binding partners in breast cancer progression and resistance to hormone and tyrosine kinase directed therapies. J. Mammary Gland Biol. Neoplasia 13(2), 225-233 (2008).
85. Aqeilan R, Donati V, Gaudio E et al.: Association of Wwox with ErbB4 in breast cancer. Cancer Res. 67(19), 9330-9336 (2007).
86. Aqeilan R, Donati V, Palamarchuk A et al.: WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 65(15), 6764-6772 (2005).
87. Law A, Kleinman J, Weinberger D, Weickert C: Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia. Hum. Mol. Genet., 16(2), 129-141 (2007).
88. Chaudhury A, Gerecke K, Wyss J, Morgan D, Gordon M, Carroll S: Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J. Neuropathol. Exp. Neurol. 62(1), 42-54 (2003).
89. Gilbertson RJ, Perry RH, Kelly PJ, Pearson AD, Lunec J: Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Res. 57(15), 3272-3280 (1997).
90. Gilbertson RJ, Bentley L, Hernan R et al.: ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin. Cancer Res. 8(10), 3054-3064 (2002).
91. Torp S, Gulati S, Johannessen E, Dalen A: Coexpression of c-erbB 1-4 receptor proteins in human glioblastomas. An immunohistochemical study. J. Exp. Clin. Cancer Res. 26(3), 353-359 (2007).
92. Laurendeau I, Ferrer M, Garrido D et al.: Gene expression profiling of ErbB receptors and ligands in human meningiomas. Cancer Invest. 27(6), 691-698 (2009).
93. Ferretti E, Di Marcotullio L, Gessi M et al.: Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets. Oncogene 25(55), 7267-7273 (2006).
94. Lee J, Wang S, Chow N, Yang H: Investigation of the prognostic value of coexpressed erbB family members for the survival of colorectal cancer patients after curative surgery. Eur. J. Cancer 38(8), 1065-1071 (2002).
95. Kountourakis P, Pavlakis K, Psyrri A et al.: Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas. BMC Cancer 6, 46 (2006).
96. Baiocchi G, Lopes A, Coudry R et al.: ErbB family immunohistochemical expression in colorectal cancer patients with higher risk of recurrence after radical surgery. Int. J. Colorectal Dis. 24(9), 1059-1068 (2009).
97. Bei R, Budillon A, Masuelli L et al.: Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J. Pathol. 204(3), 317-325 (2004).
98. Xia W, Lau Y, Zhang H et al.: Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin. Cancer Res. 5(12), 4164-4174 (1999).
99. Kassouf W, Black P, Tuziak T et al.: Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J. Urol. 179(1), 353-358 (2008).
100. Memon A, Sorensen B, Melgard P, Fokdal L, Thykjaer T, Nexo E: Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients. Br. J. Cancer 91(12), 2034-2041 (2004).
101. Wiseman S, Griffith O, Melck A et al.: Evaluation of type 1 growth factor receptor family expression in benign and malignant thyroid lesions. Am. J. Surg. 195(5), 667-673; discussion 673 (2008).
102. Merimsky O, Staroselsky A, Inbar M et al.: Correlation between c-erbB-4 receptor expression and response to gemcitabinecisplatin chemotherapy in non-small-cell lung cancer. Ann. Oncol. 12(8), 1127-1131 (2001).
103. Merimsky O, Kollender Y, Issakov J et al.: Induction chemotherapy for bone sarcoma in adults: correlation of results with erbB-4 expression. Oncol. Rep. 10(5), 1593-1599 (2003).
104. Merimsky O, Issakov J, Bickels J et al.: ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy. Eur. J. Cancer 38(10), 1335-1342 (2002).
105. Steffensen K, Waldstrøm M, Andersen R et al.: Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors. Int. J. Oncol. 33(1), 195-204 (2008).
106. Adonakis G, Androutsopoulos G, Koumoundourou D, Liava A, Ravazoula P, Kourounis G: Expression of the epidermal growth factor system in endometrial cancer. Eur. J. Gynaecol. Oncol. 29(5), 450-454 (2008).
107. Gilmour LM, Macleod KG, McCaig A, Gullick WJ, Smyth JF, Langdon SP: Expression of erbB-4/HER-4 growth factor receptor isoforms in ovarian cancer. Cancer Res. 61(5), 2169-2176 (2001).
108. Srinivasan R, Benton E, McCormick F, Thomas H, Gullick WJ: Expression of the c-erbB-3/HER-3 and c-erbB-4/HER-4 growth factor receptors and their ligands, neuregulin-1 α, neuregulin-1 β, and βcellulin, in normal endometrium and endometrial cancer. Clin. Cancer Res. 5(10), 2877-2883 (1999).
109. Ben-Yosef R, Sarid D, Vexler A et al.: Nuclear and cytoplasmic expression of ErbB-4 in prostate cancer. Int. J. Biol. Markers 22(3), 181-185 (2007).
110. Paez J, Jänne P, Lee J et al.: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676), 1497-1500 (2004). ■ Identification of EGFR mutations that sensitize lung cancer to EGFR tyrosine kinase inhibitors.
111. Pao W, Miller V, Politi K et al.: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2(3), E73 (2005).
112. Ding L, Getz G, Wheeler D et al.: Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455(7216), 1069-1075 (2008).
113. Soung Y, Lee J, Kim S et al.: Somatic mutations of the ERBB4 kinase domain in human cancers. Int. J. Cancer 118(6), 1426-1429 (2006).
114. Davies H, Hunter C, Smith R et al.: Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res. 65(17), 7591-7595 (2005).
115. Parsons D, Wang T, Samuels Y et al.: Colorectal cancer: mutations in a signalling pathway. Nature 436(7052), 792 (2005).
116. Tvorogov D, Sundvall M, Kurppa K et al.: Somatic mutations of ErbB4: selective loss-of-function phenotype affecting signal transduction pathways in cancer. J. Biol. Chem. 284(9), 5582-5591 (2009).
117. Feng S, Sartor C, Hunter D et al.: The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell proliferation. Mol. Endocrinol. 21(8), 1861-1876 (2007).
118. Sartor C, Zhou H, Kozlowska E et al.: Her4 mediates ligand-dependent antiproliferative and differentiation responses in human breast cancer cells. Mol. Cell. Biol. 21(13), 4265-4275 (2001).
119. Muraoka-Cook R, Caskey L, Sandahl M et al.: Heregulin-dependent delay in mitotic progression requires HER4 and BRCA1. Mol. Cell. Biol. 26(17), 6412-6424 (2006).
120. Zhang K, Sun J, Liu N et al.: Transformation of NIH 3T3 cells by HER3 or HER4 receptors requires the presence of HER1 or HER2. J. Biol. Chem. 271(7), 3884-3890 (1996).
121. Alaoui-Jamali M, Song D, Benlimame N et al.: Regulation of multiple tumor microenvironment markers by overexpression of single or paired combinations of ErbB receptors. Cancer Res. 63(13), 3764-3774 (2003).
122. Pitfield S, Bryant I, Penington D, Park G, Riese DN: Phosphorylation of ErbB4 on tyrosine 1056 is critical for ErbB4 coupling to inhibition of colony formation by human mammary cell lines. Oncol. Res. 16(4), 179-193 (2006).
123. Gallo R, Bryant I, Fry R, Williams E, Riese DN: Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines. Biochem. Biophys. Res. Commun. 349(1), 372-382 (2006).
124. Vidal G, Clark D, Marrero L, Jones F: A constitutively active ERBB4/HER4 allele with enhanced transcriptional coactivation and cell-killing activities. Oncogene 26(3), 462-466 (2007).
125. Jackson-Fisher A, Bellinger G, Shum E et al.: Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene 25(41), 5664-5672 (2006).
126. Tang C, Goldstein D, Payne J et al.: ErbB-4 ribozymes abolish neuregulin-induced mitogenesis. Cancer Res. 58(15), 3415-3422 (1998).
127. Jones F: HER4 intracellular domain (4ICD) activity in the developing mammary gland and breast cancer. J. Mammary Gland Biol. Neoplasia 13(2), 247-258 (2008).
128. Kang H, Jenabi J, Zhang J et al.: E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 67(7), 3094-3105 (2007).
129. Frey M, Edelblum K, Mullane M, Liang D, Polk D: The ErbB4 growth factor receptor is required for colon epithelial cell survival in the presence of TNF. Gastroenterology 136(1), 217-226 (2009).
130. Lee D, Yu M, Lee E et al.: Tumor-specific apoptosis caused by deletion of the ERBB3 pseudo-kinase in mouse intestinal epithelium. J. Clin. Invest. 119(9), 2702-2713 (2009).
131. Vexler A, Lidawi G, Loew V et al.: Anti-ERBb4 targeted therapy combined with radiation therapy in prostate cancer. Results of in vitro and in vivo studies. Cancer Biol. Ther. 7(7), 1090-1094 (2008).
132. Brodowicz T, Wiltschke C, Budinsky A, Krainer M, Steger G, Zielinski C: Soluble HER-2/neu neutralizes biologic effects of anti-HER-2/neu antibody on breast cancer cells in vitro. Int. J. Cancer 73(6), 875-879 (1997).
133. Leary A, Hanna W, van de Vijver M et al.: Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients. J. Clin. Oncol. 27(10), 1694-1705 (2009).
134. Kirkegaard T, Naresh A, Sabine V et al.: Expression of tumor necrosis factor a converting enzyme in endocrine cancers. Am. J. Clin. Pathol. 129(5), 735-743 (2008).
135. Murabito J, Rosenberg C, Finger D et al.: A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study. BMC Med. Genet. 8(Suppl. 1), S6 (2007).
136. Rokavec M, Justenhoven C, Schroth W et al.: A novel polymorphism in the promoter region of ERBB4 is associated with breast and colorectal cancer risk. Clin. Cancer Res. 13(24), 7506-7514 (2007).
137. Tovey S, Dunne B, Witton C, Cooke T, Bartlett J: HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular domains of HER4. Breast Cancer Res. 8(2), R19 (2006).
138. Pawlowski V, Révillion F, Hebbar M, Hornez L, Peyrat J: Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin. Cancer Res. 6(11), 4217-4225 (2000).
139. Leung S, Griffith O, Masoudi H et al.: Clinical utility of type 1 growth factor receptor expression in colon cancer. Am. J. Surg. 195(5), 604-610 (2008).
140. Rautava J, Jee K, Miettinen P et al.: ERBB receptors in developing, dysplastic and malignant oral epithelia. Oral Oncol. 44(3), 227-235 (2008).
141. Chang J, Tsao Y, Liu D, Han C, Lee W, Chen S: The expression of type I growth factor receptors in the squamous neoplastic changes of uterine cervix. Gynecol. Oncol. 73(1), 62-71 (1999).
142. Ejskjaer K, Sørensen B, Poulsen S, Forman A, Nexø E, Mogensen O: Expression of the epidermal growth factor system in endometrioid endometrial cancer. Gynecol. Oncol. 104(1), 158-167 (2007).
143. Amsellem-Ouazana D, Bièche I, Tozlu S, Botto H, Debré B, Lidereau R: Gene expression profiling of ERBB receptors and ligands in human transitional cell carcinoma of the bladder. J. Urol. 175(3 Pt 1), 1127-1132 (2006).
144. Chow N, Chan S, Tzai T, Ho C, Liu H: Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin. Cancer Res. 7(7), 1957-1962 (2001).
145. Sasaki H, Okuda K, Kawano O et al.: ErbB4 expression and mutation in Japanese patients with lung cancer. Clin. Lung Cancer 8(7), 429-433 (2007).