Phosphoinositide 3-kinase targeting by the beta galactoside binding protein cytokine negates akt gene expression and leads aggressive breast cancer cells to apoptotic death.

Breast Cancer Research : BCR
Valerie Wells, Livio Mallucci

Abstract

Phosphoinositide 3-kinase (PI3K)-activated signalling has a critical role in the evolution of aggressive tumourigenesis and is therefore a prime target for anticancer therapy. Previously we have shown that the beta galactoside binding protein (betaGBP) cytokine, an antiproliferative molecule, induces functional inhibition of class 1A and class 1B PI3K. Here, we have investigated whether, by targeting PI3K, betaGBP has therapeutic efficacy in aggressive breast cancer cells where strong mitogenic input is fuelled by overexpression of the ErbB2 (also known as HER/neu, for human epidermal growth factor receptor 2) oncoprotein receptor and have used immortalised ductal cells and non-aggressive mammary cancer cells, which express ErbB2 at low levels, as controls. Aggressive BT474 and SKBR3 cancer cells where ErbB2 is overexpressed, MCF10A immortalised ductal cells and non-invasive MCF-7 cancer cells which express low levels of ErbB2, both in their naive state and when forced to mimic aggressive behaviour, were used. Class IA PI3K was immunoprecipitated and the conversion of phosphatidylinositol (4,5)-biphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3) assessed by ELISA. The consequences of PI3K inhibition by betaG...Continue Reading

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Citations

Aug 23, 2011·Parasitology·Eka W SuradjiHiroshi Koyama
May 25, 2013·Cell Death and Differentiation·R G Lichtenstein, G A Rabinovich
Dec 3, 2013·Drug Discovery Today·Livio Mallucci, Valerie Wells
Mar 3, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tammy YauTzi Bun Ng
Sep 29, 2019·British Journal of Cancer·Mara CironeLivio Mallucci
Oct 28, 2019·Cancers·Linah F Al-AlemBo R Rueda
Dec 31, 2020·Animals : an Open Access Journal From MDPI·Ying ZhaoDegui Lin
Nov 6, 2021·Cancer Gene Therapy·Livio Mallucci, Valerie Wells

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Methods Mentioned

BETA
nucleotide exchange
fluorescence-activated cell sorting
immunoprecipitation
ELISA
electrophoresing

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