Adrenomedullin blockade suppresses sunitinib-resistant renal cell carcinoma growth by targeting the ERK/MAPK pathway.

ABSTRACT:

Purpose

To evaluate the mechanisms underlying sunitinib resistance in RCC and to identify targets that may be used to overcome this resistance.

Results

Reanalysis of transcriptome microarray datasets (GSE64052 and GSE76068) showed that adrenomedullin expression was increased in sunitinib-resistant tumors. And adrenomedullin expression was increased in sunitinib-resistant tumor xenografts, accompanied by upregulation of phospho-ERK levels. However, blocking adrenomedullin inhibited sunitinib-resistant tumor growth. Treatment of RCC cells with sunitinib and ADM22-52 was superior to monotherapy with either agent. Additionally, adrenomedullin upregulated cAMP and activated the ERK/MAPK pathway, promoting cell proliferation, while knockdown of adrenomedullin inhibited RCC cell gr

SUBMITTER: Gao Y 

PROVIDER: S-EPMC5325371 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature