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Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation.

Abstract：

:As tumors grow and invade beyond their homeostatic limits, the tumor cells are subjected to insufficient nutrient and oxygen supplies because of excessive demand for nutrition and oxygen, and insufficient vascularization. We therefore hypothesized that tolerance to nutrient deprivation as well as angiogenesis may be critical in some malignancies, including pancreatic cancers, which are seen to be a hypovascular tumor. In this study, we assessed the effect of AMP-activated protein kinase (AMPK), which plays a major role in protecting cells from metabolic stresses, on tumor biology under nutrient-deprived condition. Whereas hepatic cancer cells had mostly died within 48 h during glucose deprivation, most pancreatic cancer cells survived more than 48 h. The tolerance to glucose deprivation tended to correlate with the cells level of expression of AMPK alpha1 and alpha2. The introduction of AMPK antisense RNA expression vectors into pancreas cancer cell lines, PANC-1 and AsPC-1, significantly diminished their tolerance to glucose deprivation, and the stable transfection of AMPK antisense into PANC-1 cells inhibited tumor growth in nude mice. These findings indicate that AMPK expression contributes to tolerance to nutrient starvation in cancer cells. We propose AMPK as a new target for therapeutic strategies to suppress tumor growth and invasion.

journal_name

Oncogene

journal_title

Oncogene

authors

Kato K,Ogura T,Kishimoto A,Minegishi Y,Nakajima N,Miyazaki M,Esumi H

doi

10.1038/sj.onc.1205737

subject

Has Abstract

pub_date

2002-09-05 00:00:00

pages

6082-90

issue

39

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

杂志文章

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