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Oncogenic KRAS sensitises colorectal tumour cells to chemotherapy by p53-dependent induction of Noxa.


ABSTRACT:

Background

Oxaliplatin and 5-fluorouracil (5-FU) currently form the backbone of conservative treatment in patients with metastatic colorectal cancer. Tumour responses to these agents are highly variable, but the underlying mechanisms are poorly understood. Our previous results have indicated that oncogenic KRAS in colorectal tumour cells sensitises these cells to chemotherapy.

Methods

FACS analysis was used to determine cell-cycle distribution and the percentage of apoptotic and mitotic cells. A multiplexed RT-PCR assay was used to identify KRAS-controlled apoptosis regulators after exposure to 5-FU or oxaliplatin. Lentiviral expression of short-hairpin RNAs was used to suppress p53 or Noxa.

Results

Oncogenic KRAS sensitised colorectal tumour cells to oxaliplatin and

SUBMITTER: de Bruijn MT 

PROVIDER: S-EPMC2856010 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature