Insulin promotes invasion and migration of KRAS^G12D mutant HPNE cells by upregulating MMP-2 gelatinolytic activity via ERK- and PI3K-dependent signalling.

ABSTRACT:

Objectives

Hyperinsulinemia is a risk factor for pancreatic cancer, but the function of insulin in carcinogenesis is unclear, so this study aimed to elucidate the carcinogenic effects of insulin and the synergistic effect with the KRAS mutation in the early stage of pancreatic cancer.

Materials and methods

A pair of immortalized human pancreatic duct-derived cells, hTERT-HPNE E6/E7/st (HPNE) and its oncogenic KRAS^G12D variant, hTERT-HPNE E6/E7/KRAS^G12D /st (HPNE-mut-KRAS), were used to investigate the effect of insulin. Cell proliferation, migration and invasion were assessed using Cell Counting Kit-8 and transwell assays, respectively. The expression of E-cadherin, N-cadherin, vimentin and matrix metalloproteinases (MMP-2, MMP-7 and MMP-9) was evaluate

SUBMITTER: Wang G 

PROVIDER: S-EPMC6536446 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature