MEK1 and Erk1/2 kinases as targets for the modulation of radiation responses

被引：0

作者：

Belka, C ^{[1
]}

Knippers, P ^{[1
]}

Rudner, J ^{[1
]}

Faltin, H ^{[1
]}

Bamberg, M ^{[1
]}

Budach, W ^{[1
]}

机构：

[1] Univ Tubingen, Dept Radiotherapy, D-72076 Tubingen, Germany

来源：

ANTICANCER RESEARCH | 2000年 / 20卷 / 5A期

关键词：

radiation; apoptosis; Erk1/2; kinase; MEK-1; PD98059; clonogen; cell death;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The activation of mitogenic cascades via Ras, c-Raf-1, MEK-1, Erk1/2 is a hall- mark of oncogenic transformation. The cascade is also anti-apoptotic by modulation of Bcl-2, Bcl-x(L) and BAD function. The impact of MEK-1 on radiation resistance and the role of drugs targeting MEK-1 for the modulation of resistance is unclear. Materials and Methods: Activation of MEK-2 in four carcinoma cell lines was analyzed using Erk1/2 phosphospecific antibodies. MEK-1 was blocked by PD98059 (2-amino-3methoxyflavin) and influence on radiation responses was determined by apoptotic morphology, caspase-3 activation and colony formation assays. Results: MEK-1 kinase was constitutively active and inhibitable by PD98059. The low radiation induced apoptosis rate was not increased by MEK inhibition. PD98059 did not influence cell growth and radiation induced, clonogenic cell death. Conclusion: Since PD98059 did not alter radiation responses despite blocking MEK-1 kinase, MEK-1 and Erk1/2 are not involved in radiation resistance. Thus PD98059 has no potential in the modulation of radiation responses.

引用

页码：3243 / 3249

页数：7

共 31 条

[11] A SYNTHETIC INHIBITOR OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CASCADE [J].

DUDLEY, DT ;

PANG, L ;

DECKER, SJ ;

BRIDGES, AJ ;

SALTIEL, AR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7686-7689

[12] Energy metabolism during apoptosis - bcl-2 promotes survival in hematopoietic cells induced to apoptose by growth factor withdrawal by stabilizing a form of metabolic arrest [J].

Garland, JM ;

Halestrap, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (08) :4680-4688

[13] PHOSPHORYLATION OF TRANSCRIPTION FACTOR P62TCF BY MAP KINASE STIMULATES TERNARY COMPLEX-FORMATION AT C-FOS PROMOTER [J].

GILLE, H ;

SHARROCKS, AD ;

SHAW, PE .

NATURE, 1992, 358 (6385) :414-417

[14] RAF-1 FORMS A STABLE COMPLEX WITH MEK1 AND ACTIVATES MEK1 BY SERINE PHOSPHORYLATION [J].

HUANG, WD ;

ALESSANDRINI, A ;

CREWS, CM ;

ERIKSON, RL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :10947-10951

[15] ACTIVATION OF TERNARY COMPLEX FACTOR ELK-1 BY MAP KINASES [J].

JANKNECHT, R ;

ERNST, WH ;

PINGOUD, V ;

NORDHEIM, A .

EMBO JOURNAL, 1993, 12 (13) :5097-5104

[16]

LEEVERS RJ, 1994, NATURE, V369

[17]

MCKENNA WG, 1990, CANCER RES, V50, P97

[18] DIFFERENTIAL ACTIVATION OF ERK AND JNK MITOGEN-ACTIVATED PROTEIN-KINASES BY RAF-1 AND MEKK [J].

MINDEN, A ;

LIN, A ;

MCMAHON, M ;

LANGECARTER, C ;

DERIJARD, B ;

DAVIS, RJ ;

JOHNSON, GL ;

KARIN, M .

SCIENCE, 1994, 266 (5191) :1719-1723

[19] MUTATIONS AND ALTERED EXPRESSION OF P16(INK4) IN HUMAN CANCER [J].

OKAMOTO, A ;

DEMETRICK, DJ ;

SPILLARE, EA ;

HAGIWARA, K ;

HUSSAIN, SP ;

BENNETT, WP ;

FORRESTER, K ;

GERWIN, B ;

SERRANO, M ;

BEACH, DH ;

HARRIS, CC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (23) :11045-11049

[20] MUTATIONAL ACTIVATION OF THE K-RAS ONCOGENE - A POSSIBLE PATHOGENETIC FACTOR IN ADENOCARCINOMA OF THE LUNG [J].

RODENHUIS, S ;

VANDEWETERING, ML ;

MOOI, WJ ;

EVERS, SG ;

VANZANDWIJK, N ;

BOS, JL .

NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (15) :929-935

← 1 2 3 4 →