MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

Author(s)
Oliver, Trudy; Mercer, Kim L.; Sayles, Leanne C.; Burke, James R.; Mendus, Diana; Lovejoy, Katherine S.; Cheng, Mei-Hsin; Subramanian, Aravind; Mu, David; Powers, Scott; Crowley, Denise G.; Bronson, Roderick T.; Whittaker, Charles A.; Bhutkar, Arjun (AJ); Lippard, Stephen J.; Golub, Todd R.; Thomale, Juergen; Jacks, Tyler E.; Sweet-Cordero, E. Alejandro; ... Show more Show less
Thumbnail
Downloadoliver et al genes devel.pdf (357.6Kb)
OPEN_ACCESS_POLICY

Open Access Policy

Creative Commons Attribution-Noncommercial-Share Alike

Terms of use
Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/
Metadata
Show full item record
Abstract
Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.
Date issued
2010-03
URI
http://hdl.handle.net/1721.1/64761
Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry; Koch Institute for Integrative Cancer Research at MIT
Journal
Genes and Development
Publisher
Cold Spring Harbor Laboratory Press in association with The Genetics Society
Citation
Oliver, Trudy G. et al. “Chronic Cisplatin Treatment Promotes Enhanced Damage Repair and Tumor Progression in a Mouse Model of Lung Cancer.” Genes & Development 24.8 (2010) : 837 -852.
Version: Author's final manuscript
ISSN
0890-9369
1549-5477

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.