The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis

被引:157
作者
Eceles, SA [1 ]
机构
[1] Inst Canc Res, CRC Ctr Canc Therapeut, McElwain Labs, Sutton SM2 5NG, Surrey, England
关键词
HER2/neu/c-erbB-2; invasion; metastasis; drug resistance; angiogenesis; signaling pathways;
D O I
10.1023/A:1014730829872
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gene amplification and/or overexpression of the c-erbB-2/HER2/neu tyrosine kinase are linked with poor prognosis in breast cancer. This is manifest in shorter disease-free intervals, increased risk of metastasis. and resistance to many types of therapy. The molecular mechanisms and signaling circuitry underlying these phenomena are now being elucidated. c-erbB-2, although having no known soluble ligand, is transactivated by heterodimerization with other family members (EGFR. c-erbB-3. c-erbB-4). Receptor activation potentiates tumor cell motility, protease secretion and invasion, and also modulates cell cycle checkpoint function, DNA repair, and apoptotic responses. Since it is expressed at low levels in normal adult tissues, c-erbB-2 is an ideal target for therapy. There is reason for optimism that agents targeting c-erbB-2 signaling will have profound and selective effects in breast cancer, either as single agents or more likely in combination with other therapeutic agents, to enhance their potency.
引用
收藏
页码:393 / 406
页数:14
相关论文
共 76 条
  • [1] Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase
    Adam, L
    Vadlamudi, R
    Kondapaka, SB
    Chernoff, J
    Mendelsohn, J
    Kumar, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) : 28238 - 28246
  • [2] Stimulation of β1-integrin function by epidermal growth factor and heregulin-β has distinct requirements for erbB2 but a similar dependence on phosphoinositide 3-OH kinase
    Adelsman, MA
    McCarthy, JB
    Shimizu, Y
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (09) : 2861 - 2878
  • [3] The role of ErbB-2 tyrosine kinase receptor in cellular intrinsic chemoresistance: mechanisms and implications
    Alaoui-Jamali, MA
    Paterson, J
    Al Moustafa, AE
    Yen, L
    [J]. BIOCHEMISTRY AND CELL BIOLOGY, 1997, 75 (04) : 315 - 325
  • [4] Vascular endothelial growth factor up-regulation via p21-activated kinase-1 signaling regulates heregulin-β1-mediated angiogenesis
    Bagheri-Yarmand, R
    Vadlamudi, RK
    Wang, RA
    Mendelsohn, J
    Kumar, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (50) : 39451 - 39457
  • [5] Interactions between progestins and heregulin (HRG) signaling pathways:: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
    Balañá, ME
    Lupu, R
    Labriola, L
    Charreau, EH
    Elizalde, PV
    [J]. ONCOGENE, 1999, 18 (46) : 6370 - 6379
  • [6] Brandt B, 1998, INT J CANCER, V76, P824, DOI 10.1002/(SICI)1097-0215(19980610)76:6<824::AID-IJC10>3.0.CO
  • [7] 2-2
  • [8] c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells
    Brandt, BH
    Roetger, A
    Dittmar, T
    Nikolai, G
    Seeling, M
    Merschjann, A
    Nofer, JR
    Dehmer-Möller, G
    Junker, R
    Assmann, G
    Zaenker, KS
    [J]. FASEB JOURNAL, 1999, 13 (14) : 1939 - 1949
  • [9] Braun S, 2001, CANCER RES, V61, P1890
  • [10] Burke HB, 1998, CANCER-AM CANCER SOC, V82, P874, DOI 10.1002/(SICI)1097-0142(19980301)82:5<874::AID-CNCR11>3.0.CO