her2 overexpression seems to make breast cancer cells insulin-independent
 

ie they do not require it for growth or survival

her2 amplification seems to change metabolism of breast cancer cells as described below--
PLoS One. 2011 Mar 17;6(3):e17959.
Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.
Bollig-Fischer A, Dewey TG, Ethier SP.

Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
Abstract
Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF10A cells to an insulin-independent phenotype. Analysis of the effects of various concentrations of insulin and/or IGF-I on proliferation of MCF10A cells demonstrated that some of the effects of insulin were independent from those of IGF-I, suggesting that oncogene over expression drives a true insulin-independent proliferative phenotype. To test this hypothesis, we examined metabolic functions of insulin signaling in insulin-dependent and insulin-independent cells. HER2 over expression in MCF10A cells resulted in glucose uptake in the absence of insulin at a rate equal to insulin-induced glucose uptake in non-transduced cells. We found that a diverse set of oncogenes induced the same result. To gain insight into how HER2 oncogene signaling affected increased insulin-independent glucose uptake we compared HER2-regulated gene expression signatures in MCF10A and HER2 over expressing MCF10A cells by differential analysis of time series gene expression data from cells treated with a HER2 inhibitor. This analysis identified genes specifically regulated by the HER2 oncogene, including VAMP8 and PHGDH, which have known functions in glucose uptake and processing of glycolytic intermediates, respectively. Moreover, these genes specifically implicated in HER2 oncogene-driven transformation are commonly altered in human breast cancer cells. These results highlight the diversity of oncogene effects on cell regulatory pathways and the importance of oncogene-driven metabolic transformation in breast cancer.

PMID: 21437235

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

what does this mean?

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

ie they do not require it for growth or survival

Many breast cancer cells do, but once they transform and become her2+ they no longer do, their metabolism changes

Since her2+ breast cancer (we suppose as the cell lines often, but not always reflect behavior in the body) has a different metabolism than other breast cancers, so saying one drug or diet or treatment which helps/worsens ALL BREAST CANCERS (which is what most articles discuss) may not necessarily be true for her2+ bc.

IGFR1 inhibition may be helpful in some her2+ breast cancers which become resistant to hercetin, but we don't necessariy understand the mechanism and there are IRs and IGFRs (insulin receptors and insulin-like growth factor receptors)

Again, it is not a simple story, but the take-home message is her2+ breast cancer may have a metabolism that is different from other breast cancers so look for articles where her2+ breast cancer or cell lines were specifically studied. eg SKBR3, BT-474

Hope this helped!

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

I remember my first onc saying that ER+ may use insulin but he doubted that her 2+ did. Looks like he may have been right!Guess this has implications for dietary issues/controls?

Ellie

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

Yikes...I am now considered a pre-stage type 2 diabetic...go figure

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

Thank Lani...

Re: her2 overexpression seems to make breast cancer cells insulin-independent
 

Thanks Lani
So does this mean we can eat chocolate! lol!
health and happiness
sarah