Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression.

ABSTRACT: Poorly differentiated tumors of the thyroid gland (PDTC) are generally characterized by a poor prognosis due to their resistance to available therapeutic approaches. The relative rarity of these tumors is a major obstacle to our understanding of the molecular mechanisms leading to tumor aggressiveness and drug resistance, and consequently to the development of novel therapies. By simultaneously activating Kras and deleting p53 (Trp53) in thyroid follicular cells, we have generated a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC. In several cases, tumors further progress to anaplastic carcinomas. The poorly differentiated tumors are morphologically and functionally similar to their human counterparts and depend on MEK/ERK signaling for proliferation

SUBMITTER: Champa D 

PROVIDER: S-EPMC4152557 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature