Linked Life Data

21102522

Source:http://linkedlifedata.com/resource/pubmed/id/21102522

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-3-10
pubmed:abstractText
Hypothesis-generating epidemiological research has suggested that cancer burden is reduced in diabetics treated with metformin and experimental work has raised questions regarding the role of direct adenosine monophosphate-activated protein kinase (AMPK)-mediated anti-neoplastic effects of metformin as compared with indirect effects attributable to reductions in circulating insulin levels in the host. We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor. Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin. These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:copyrightInfo
© 2011 Macmillan Publishers Limited
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1174-82
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo.
pubmed:affiliation
E423 Segal Cancer Centre of the Jewish General Hospital, Departments of Experimental Medicine and Oncology, McGill University, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't