Susceptibility of ATM-deficient pancreatic cancer cells to radiation

被引:28
作者
Ayars, Michael [1 ]
Eshleman, James [1 ,2 ]
Goggins, Michael [1 ,2 ,3 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA
关键词
ATM; pancreatic cancer; radiosensitivity; STEREOTACTIC BODY RADIOTHERAPY; CHRONIC LYMPHOCYTIC-LEUKEMIA; PREDISPOSITION GENES; PROTEIN EXPRESSION; CELLULAR-RESPONSE; DNA-REPAIR; PHASE-II; IN-VITRO; MUTATIONS; SURVIVAL;
D O I
10.1080/15384101.2017.1312236
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.
引用
收藏
页码:991 / 998
页数:8
相关论文
共 44 条
[1]  
[Anonymous], ONCOTARGET
[2]  
[Anonymous], ONCOTARGET
[3]   Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion [J].
Austen, Belinda ;
Skowronska, Anna ;
Baker, Claire ;
Powell, Judith E. ;
Gardiner, Anne ;
Oscier, David ;
Majid, Aneela ;
Dyer, Martin ;
Siebert, Reiner ;
Taylor, A. Malcolm ;
Moss, Paul A. ;
Stankovic, Tatjana .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (34) :5448-5457
[4]   DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].
Bakkenist, CJ ;
Kastan, MB .
NATURE, 2003, 421 (6922) :499-506
[5]   Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer [J].
Bang, Yung-Jue ;
Im, Seock-Ah ;
Lee, Keun-Wook ;
Cho, Jae Yong ;
Song, Eun-Kee ;
Lee, Kyung Hee ;
Kim, Yeul Hong ;
Park, Joon Oh ;
Chun, Hoo Geun ;
Zang, Dae Young ;
Fielding, Anitra ;
Rowbottom, Jacqui ;
Hodgson, Darren ;
O'Connor, Mark J. ;
Yin, Xiaolu ;
Kim, Woo Ho .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (33) :3858-+
[6]   Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].
Biankin, Andrew V. ;
Waddell, Nicola ;
Kassahn, Karin S. ;
Gingras, Marie-Claude ;
Muthuswamy, Lakshmi B. ;
Johns, Amber L. ;
Miller, David K. ;
Wilson, Peter J. ;
Patch, Ann-Marie ;
Wu, Jianmin ;
Chang, David K. ;
Cowley, Mark J. ;
Gardiner, Brooke B. ;
Song, Sarah ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Nourse, Craig ;
Nourbakhsh, Ehsan ;
Manning, Suzanne ;
Wani, Shivangi ;
Gongora, Milena ;
Pajic, Marina ;
Scarlett, Christopher J. ;
Gill, Anthony J. ;
Pinho, Andreia V. ;
Rooman, Ilse ;
Anderson, Matthew ;
Holmes, Oliver ;
Leonard, Conrad ;
Taylor, Darrin ;
Wood, Scott ;
Xu, Qinying ;
Nones, Katia ;
Fink, J. Lynn ;
Christ, Angelika ;
Bruxner, Tim ;
Cloonan, Nicole ;
Kolle, Gabriel ;
Newell, Felicity ;
Pinese, Mark ;
Mead, R. Scott ;
Humphris, Jeremy L. ;
Kaplan, Warren ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chou, Angela ;
Chin, Venessa T. ;
Chantrill, Lorraine A. .
NATURE, 2012, 491 (7424) :399-405
[7]   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
[8]   Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated [J].
Chuong, Michael D. ;
Springett, Gregory M. ;
Freilich, Jessica M. ;
Park, Catherine K. ;
Weber, Jill M. ;
Mellon, Eric A. ;
Hodul, Pamela J. ;
Malafa, Mokenge P. ;
Meredith, Kenneth L. ;
Hoffe, Sarah E. ;
Shridhar, Ravi .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2013, 86 (03) :516-522
[9]   Genetically Defined Subsets of Human Pancreatic Cancer Show Unique In Vitro Chemosensitivity [J].
Cui, Yunfeng ;
Brosnan, Jacqueline A. ;
Blackford, Amanda L. ;
Sur, Surojit ;
Hruban, Ralph H. ;
Kinzler, Kenneth W. ;
Vogelstein, Bert ;
Maitra, Anirban ;
Diaz, Luis A., Jr. ;
Iacobuzio-Donahue, Christine A. ;
Eshleman, James R. .
CLINICAL CANCER RESEARCH, 2012, 18 (23) :6519-6530
[10]   Comparison of EUS-guided tissue acquisition using two different 19-gauge core biopsy needles: a multicenter, prospective, randomized, and blinded study [J].
DeWitt, John ;
Cho, Chang-Min ;
Lin, Jingmei ;
Al-Haddad, Mohammad ;
Canto, Marcia Irene ;
Salamone, Ashley ;
Hruban, Ralph H. ;
Messallam, Ahmed A. ;
Khashab, Mouen A. .
ENDOSCOPY INTERNATIONAL OPEN, 2015, 3 (05) :E471-E478