More about the importance of lipid rafts ^ (see previous post) and the possibility they have a very special role in HER2
This explains the active HER2 receptors (Docking stations built into the cells outer wall (membrane) into which the HER2 protein fits like a key) are only found in a particular areas of the double skin fat/protein/cholesterol bubbles that form the outer layer of cells (think bubble). The particular areas in which active HER2 receptors are apparently exclusively found are called lipid rafts (Special functional areas within the surface of the bubble that contain greater amounts of close packed fats)
It also explains that the docking locks come in three types, on activated by one HER2 protein (monomer), another type by a pair of HER2s (homodimer) and a third by an HER2 combined with another, probably specific, substance (heterodimer).
The results also suggest that there may be a connection between an increased number of HER2 docking locks and more numerous areas of lipid rafts in the cell membrane.
The HER2 protein may look something like this
http://en.wikipedia.org/wiki/File:Tr...mplex_1N8Z.png see Wikipedia http://en.wikipedia.org/wiki/HER2/neu
The paper explains DHA may alter the structure of the rafts so possibly disrupting the docking locks which ultimately may lead to higher cell death rates in cells expressing more HER2 receptors.
ABSTRACT
http://www.ncbi.nlm.nih.gov/pubmed/22749134
J Nutr Biochem. 2012 Jun 27. [Epub ahead of print]
Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression.
Ravacci GR, Brentani MM, Tortelli T Jr, Torrinhas RS, Saldanha T, Torres EA, Waitzberg DL.
Source
Department of Oncology Medical School, University of São Paulo, 01246-903 São Paulo, Brazil; Department of Gastroenterology Medical School, University of São Paulo-LIM 35, 01246-903 São Paulo, Brazil.
Abstract
In HER-2-overexpressing breast cells, HER-2 receptors exist on the cell surface as monomers, homodimers and heterodimers. For signal activation and transduction to occur, HER-2 must be localized to lipid rafts. Therefore, we hypothesized that the amount of lipid rafts on the cell membrane would be a factor in HER-2 signaling. To test this, we used HB4a (an untransformed human mammary epithelial cell line) and HB4aC5.2 cells.
HB4aC5.2 cells are HB4a derivatives that have been transfected with five copies of pJ5E.c-ErbB-2 and express approximately 900 times more HER-2 than HB4a cells. In these cells, HER-2 overexpression was accompanied by increased lipid rafts in cell membranes, a hyperactivation of downstream Akt and ERK1/2 proteins, and an increased rate of cell growth compared to HB4a. In addition, HER-2 overexpression was associated with an increased activation of FASN, a key enzyme involved in cellular lipogenesis. Its final product, palmitate, is frequently used to synthesize lipid rafts.
We further hypothesized that treatment with docosahexaenoic acid (DHA), an omega-3 fatty acid, would disrupt the lipid rafts and lead to a growth arrest. In HB4aC5.2 cells, but not HB4a cells, we found that DHA treatment disrupted lipid raft; inhibited HER-2 signaling by decreasing activation of Akt, ERK1/2 and FASN proteins; and induced apoptosis.
Although little is known about lipid rafts, our data support the idea that disturbances in these microdomains induced by DHA may represent a useful tool for controlling the signaling initiated by HER-2 receptors and its therapeutic potential in the treatment of HER-2 positive breast cancer.
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