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Old 01-08-2009, 03:24 PM   #1
Lani
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Join Date: Mar 2006
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the holy Grail? The body has its own inbuilt PI3K inhibitor that causes massive cell

death of breast cancer cells overexpressing her2

Al from Canada once asked if there wasn't a natural PI3K inhibitor--now it turns out there is one already in the body on certain immune cells and even normal body cells and that it is exquisitely effective against her2 overexpressing breast cancers--now they have to figure out how to harvest it and get it in the right place at the right time

The article is open access at Breast Cancer Research http://breast-cancer-research.com/content/11/1/R2

Research article
PI3K targeting by the beta-GBP cytokine negates akt gene expression and leads aggressive breast cancer cells to apoptotic death
Valerie Wells and Livio Mallucci

Breast Cancer Research 2009, 11:R2doi:10.1186/bcr2217

Published: 8 January 2009
Abstract

Introduction
PI3K activated signaling has a critical role in the evolution of aggressive tumorigenesis and is therefore a prime target for anti-cancer therapy. In previous work we have shown that the beta galactoside binding protein (betaGBP) cytokine, an anti-proliferative 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 oncoprotein receptor and have used as controls immortalised ductal cells and non aggressive mammary cancer cells, which express ErbB2 at low levels.

Methods
Cells used: 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. Class IA PI3K was immunoprecipitated and the conversion of PIP2 to PIP3 assessed in a competitive ELISA. The consequences of PI3K inhibition by betaGBP were analysed at proliferation level, ERK activation, akt gene expression and apoptosis. Apoptosis was documented by changes in mitochondrial membrane potential, alteration of the plasma membrane, caspase 3 activation and DNA fragmentation. Phosphorylated and total ERK were measured by Western blot analysis and akt mRNA levels by Northern blot analysis. The results obtained with the BT474 and SKBR3 cells were validated in the MCF10A ductal cells and in non-invasive MCF-7 breast cancer cells forced into mimicking the in vitro behaviour of the BT474 and SKBR3 cells.

Results
We report that in aggressive breast cancer cells, where mitogenic signaling is enforced by the ErbB2 oncoprotein receptor, functional inhibition of the catalytic activity of PI3K by the betaGBP cytokine and loss of akt mRNA results in apoptotic death. We also report a functional correlation between ERK and the akt gene. The relationship between ERK, akt mRNA, PI3K and cell vulnerability to GBP challenge was sustained both in mammary ductal cells forced to mimic an aggressive behaviour and in non aggressive breast cancer cells undergoing an enforced shift into an aggressive phenotype.

Conclusions
betaGBP, a newly discovered physiological inhibitor of PI3K, is a selective and potent inducer of apoptosis in aggressive breast cancer cells. Due to its physiological nature, which carries no chemotherapeutic disadvantages, betaGBP has the potential to be safely tested in clinical trials.
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Old 01-08-2009, 03:49 PM   #2
eric
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Thanks Lani. I look forward to seeing the trials launch and watching for the results. Eric
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Old 01-08-2009, 07:19 PM   #3
Becky
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Selenium is a P13K inhibitor. The problem with that and vandenium is that too much is poisonous.

I wonder if the body needs adequate stores of these to build these natural inhibitors.

Good article.
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Becky

Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia

NED 18 years!

Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
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