Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition

被引：286

作者：

Krawczyk, Przemek M. ^{[2
]}

Eppink, Berina ^{[1
]}

Essers, Jeroen ^{[1
,3
,4
]}

Stap, Jan ^{[2
]}

Rodermond, Hans ^{[5
,6
]}

Odijk, Hanny ^{[1
]}

Zelensky, Alex ^{[1
]}

van Bree, Chris ^{[5
,6
]}

Stalpers, Lukas J. ^{[7
]}

Buist, Marrije R. ^{[8
]}

Soullie, Thomas ^{[9
]}

Rens, Joost ^{[9
]}

Verhagen, Hence J. M. ^{[4
]}

O'Connor, Mark J. ^{[10
]}

Franken, Nicolaas A. P. ^{[5
,6
,7
]}

ten Hagen, Timo L. M. ^{[9
]}

Kanaar, Roland ^{[1
,3
]}

Aten, Jacob A. ^{[2
]}

机构：

[1] Erasmus MC, Dept Cell Biol & Genet, Canc Genom Ctr, NL-3000 CA Rotterdam, Netherlands

[2] Univ Amsterdam, Van Leeuwenhoek Ctr Adv Microscopy LCAM AMC, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands

[3] Erasmus MC, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Vasc Surg, NL-3000 CA Rotterdam, Netherlands

[5] Univ Amsterdam, Lab Expt Oncol & Radiobiol, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands

[6] Univ Amsterdam, Dept Radiotherapy, NL-1105 AZ Amsterdam, Netherlands

[7] Univ Amsterdam, Dept Radiat Oncol, NL-1105 AZ Amsterdam, Netherlands

[8] Univ Amsterdam, Acad Med Ctr, Dept Gynecol Oncol, NL-1105 AZ Amsterdam, Netherlands

[9] Erasmus MC, Dept Surg Oncol, NL-3000 CA Rotterdam, Netherlands

[10] AstraZeneca, Canc Biosci, Alderley Pk SK10 4TG, Cheshire, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 24期

关键词：

anti-cancer treatment; RAD51; double-strand break; SISTER-CHROMATID EXCHANGES; DNA-DAMAGE; THERMAL RADIOSENSITIZATION; NUDE-MICE; PHASE-I; REPAIR; MUTANT; MECHANISM; PATHWAYS; COMBINATION;

D O I：

10.1073/pnas.1101053108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Defective homologous recombination (HR) DNA repair imposed by BRCA1 or BRCA2 deficiency sensitizes cells to poly (ADP-ribose) polymerase (PARP)-1 inhibition and is currently exploited in clinical treatment of HR-deficient tumors. Here we show that mild hyperthermia (41-42.5 degrees C) induces degradation of BRCA2 and inhibits HR. We demonstrate that hyperthermia can be used to sensitize innately HR-proficient tumor cells to PARP-1 inhibitors and that this effect can be enhanced by heat shock protein inhibition. Our results, obtained from cell lines and in vivo tumor models, enable the design of unique therapeutic strategies involving localized on-demand induction of HR deficiency, an approach that we term induced synthetic lethality.

引用

页码：9851 / 9856

页数：6

共 47 条

[1] EXPERIMENTAL RADIOTHERAPY OF A RAT RHABDOMYOSARCOMA WITH 15 MEV NEUTRONS AND 300 KV X-RAYS .I. EFFECTS OF SINGLE EXPOSURES [J].

BARENDSEN, GW ;

BROERSE, JJ .

EUROPEAN JOURNAL OF CANCER, 1969, 5 (04) :373-+

[2] Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks [J].

Bekker-Jensen, S ;

Lukas, C ;

Kitagawa, R ;

Melander, F ;

Kastan, MB ;

Bartek, J ;

Lukas, J .

JOURNAL OF CELL BIOLOGY, 2006, 173 (02) :195-206

[3] Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro [J].

Bowman, KJ ;

Newell, DR ;

Calvert, AH ;

Curtin, NJ .

BRITISH JOURNAL OF CANCER, 2001, 84 (01) :106-112

[4] Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].

Bryant, HE ;

Schultz, N ;

Thomas, HD ;

Parker, KM ;

Flower, D ;

Lopez, E ;

Kyle, S ;

Meuth, M ;

Curtin, NJ ;

Helleday, T .

NATURE, 2005, 434 (7035) :913-917

[5] Mutation of the mouse Rad17 gene leads to embryonic lethality and reveals a role in DNA damage-dependent recombination [J].

Budzowska, M ;

Jaspers, I ;

Essers, J ;

de Waard, H ;

van Drunen, E ;

Hanada, K ;

Beverloo, B ;

Hendriks, RW ;

de Klein, A ;

Kanaar, R ;

Hoeijmakers, JH ;

Maas, A .

EMBO JOURNAL, 2004, 23 (17) :3548-3558

[6] Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures [J].

Chen, Zhucheng ;

Yang, Haijuan ;

Pavletich, Nikola P. .

NATURE, 2008, 453 (7194) :489-U3

[7] The Mre11 complex: At the crossroads of DNA repair and checkpoint signalling [J].

D'Amours, D ;

Jackson, SP .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (05) :317-327

[8] DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair pathways [J].

de Jager, M ;

Dronkert, MLG ;

Modesti, M ;

Beerens, CEMT ;

Kanaar, R ;

van Gent, DC .

NUCLEIC ACIDS RESEARCH, 2001, 29 (06) :1317-1325

[9] Inhibition of Hsp90 compromises the DNA damage response to radiation [J].

Dote, Hideaki ;

Burgan, William E. ;

Camphausen, Kevin ;

Tofilon, Philip J. .

CANCER RESEARCH, 2006, 66 (18) :9211-9220

[10] The non-homologous end-joining pathway is not involved in the radiosensitization of mammalian cells by heat shock [J].

Dynlacht, JR ;

Bittner, ME ;

Bethel, JA ;

Beck, BD .

JOURNAL OF CELLULAR PHYSIOLOGY, 2003, 196 (03) :557-564

← 1 2 3 4 5 →