Dr. Cristina Tognon, a Research Scientist in Dr. Sorensen’s laboratory, recently published a new paper in the journal Cancer Research on the role of the insulin receptor and related proteins in secretory breast cancer.
“ETV6-NTRK3-Mediated Breast Epithelial Cell Transformation is Blocked by Targeting the IGF1R Signaling Pathway” – Tognon CE, Somasiri AM, Evdokimova VE, Trigo G, Uy EE, Melnyk N, Carboni JM, Gottardis MM, Roskelley CD, Pollak M, Sorensen PH. Cancer Res.2010 Dec 13. [Epub ahead of print]
Dr. Tognon’s work focuses on a subset of breast cancers that are caused by a fusion between two genes, known as ETV6-NTRK3 (EN). EN was first identified in childhood tumors, and has since been found to be the driving factor in secretory breast carcinoma (SBC). SBC is an unusual type of breast cancer as it occurs more commonly in young patients, although it can also occur in adults.
The Cancer Research paper describes a number of cancer model systems that were created in order to study the effects of EN on the ability of breast cells to divide and survive. The authors found that the differences between normal and EN-containing cancer cells could only be seen when the cells were grown in a certain way – namely, in a ball of cells inside a gel that contains the same mix of proteins in which breast cells grow in the human body. The EN cells continued to divide after the control (normal) cells had stopped, filling in the normally hollow center of the ball of cells.
When the research team took a look at how fast the EN cells moved – using time-lapse imaging and software that tracks the movements of individual cells – they found that the EN cells were not that different from control cells. These results were also confirmed by implanting labeled cells into mouse breast tissue and tracking their movement.
Taken together, these results suggest that EN tumor cells growing in these artificial model systems do not have the capacity to migrate to any significant extent. Since EN-driven tumors that occur in patients rarely move away from their original site within the breast, this suggests that the model system mimics the cancer found in humans and can therefore be used to study SBC and test new drugs.
After creating and evaluating the model system, Dr. Tognon went on to assess the effects on EN cells of blocking the insulin-like growth factor 1 (IGF1) pathway. In previous work performed in Dr. Sorensen’s lab it was discovered that the IGF1 receptor – the protein that recognizes the growth factor and passes its message on to the rest of the cell – is absolutely required for the EN fusion protein to cause its cancer-like changes. In other words, without the IGF1R protein, the EN fusion gene cannot cause cancer. Dr. Tognon was able to show that EN also needs IGF1R to change the way cells behave in the model system; EN cannot induce these changes if either the production or the function of IGF1R is blocked.
These results strongly encourage the evaluation of drugs that block the IGF1 and insulin receptors to control the growth of EN-containing cells, a line of investigation that will hopefully lead to new treatments for patients with SBC.
Post by C. Tognon and C. Ennis
The work described in the Cancer Research paper was funded by a ReThink Breast Cancer Career Development Award to Dr. Tognon; a Canadian Institutes of Health Research (CIHR) grant to Dr. Sorensen; and a Michael Smith Foundation for Health Research Graduate Student Award to co-author Aruna Somasiri.