Na+/H+ exchanger regulatory factor 1 inhibits platelet-derived growth factor signaling in breast cancer cells

Breast Cancer Research : BCR
Yong PanJia Le Dai

Abstract

The gene encoding Na+/H+ exchanger regulatory factor 1 (NHERF1) is a putative tumor suppressor gene that harbors frequent loss of heterozygosity (LOH) and intragenic mutations in breast carcinoma. The exact biologic activity of NHERF1 in mammary glands, however, remains unclear. It was recently proposed that NHERF1 forms a ternary complex with platelet-derived growth factor receptor (PDGFR) and phosphatase and tensin homolog (PTEN), linking NHERF1 suppressor activity to PDGF-initiated phosphoinositide-3 kinase (PI3K)/PTEN signaling. The effect of NHERF1 on the kinetics of PDGF-induced Akt activation was determined in cells with varied NHERF1 background. Levels of active Akt in mammary gland of NHERF1 knockout and wild-type mice were compared. We also examined how NHERF1 expression status affects cell sensitivity to PDGFR inhibitor. A plausible connection between NHERF1 and PTEN pathway was explored at the genetic level. We showed that NHERF1, through its PDZ-I domain, interacts directly with the carboxyl-terminal tail of PTEN. Knocking down NHERF1 expression in Zr75.1 cells markedly delayed the turnover of PDGF-induced phospho-Akt. Conversely, NHERF1 over-expression in MCF10A cells led to accelerated phospho-Akt degradation. Th...Continue Reading

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Jan 5, 2011·Breast Cancer Research and Treatment·Thomas KarnAchim Rody
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Oct 29, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Gyun Jee SongAlessandro Bisello
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Aug 12, 2016·International Journal of Oncology·Zhiqiang PengJunfang Zheng
Jun 24, 2021·American Journal of Physiology. Cell Physiology·Fan BaoTian-Rui Xu

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Methods Mentioned

BETA
PCR
genotyping
pull-down
in vitro transcription
pull down
immunoprecipitation

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