Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells

Previous studies demonstrated a direct correlation with loss of kangai-1 (KAI1), a metastasis suppressor, and poor prognosis in human prostate and other cancers. In this study, we have characterized the age-dependent downregulation of KAI1 in the TRAMP model which was reversed when mice were fed a g...

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Veröffentlicht in:Biochemical and biophysical research communications 2007-09, Vol.361 (1), p.169-175
Hauptverfasser: El Touny, Lara H., Banerjee, Partha P.
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description Previous studies demonstrated a direct correlation with loss of kangai-1 (KAI1), a metastasis suppressor, and poor prognosis in human prostate and other cancers. In this study, we have characterized the age-dependent downregulation of KAI1 in the TRAMP model which was reversed when mice were fed a genistein-enriched diet. We demonstrated here that doses of genistein (5 and 10 μM)—achievable by supplement intake—significantly induced the expression of KAI1, both at the mRNA and protein levels (up to 2.5-fold), and decreased the invasiveness of TRAMP-C2 cells >2.0-fold. We have pinpointed KAI1 as the invasion suppressor, since its knockdown by siRNA restored the invasive potential of genistein-treated TRAMP-C2 cells to control levels. This work provides the first evidence that genistein treatment may counteract KAI1 downregulation, which is observed in many cancer types and therefore, could be used in anti-metastatic therapies.
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subjects Age Factors
Animals
Anticarcinogenic Agents - pharmacology
CD82
Cell Line, Tumor
Disease Progression
Genistein
Genistein - pharmacology
KAI1/kangai
Kangai-1 Protein - antagonists & inhibitors
Kangai-1 Protein - biosynthesis
Kangai-1 Protein - genetics
Male
Metastasis
Mice
Neoplasm Invasiveness
Phytoestrogen
Prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
RNA Interference
TRAMP
title Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells
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