Investigating the Role of PTEN in Ewing Sarcoma (2012)
Undergraduates: Andres Rojas, Nick Gomez, Mukund Patel, Sam Wu
Faculty Advisor: Ian Davis
Department: Biology
Ewing Sarcoma, a bone and soft tissue cancer, is the second most prevalent sarcoma among children and young adults. The tumor suppressor PTEN has been shown to regulate the IGF-1/Akt signaling pathway, which promotes cell survival and proliferation. PTEN mutations are common in cancer but have yet to be investigated in Ewing Sarcoma.
We assayed seven Ewing cell lines and twenty primary Ewing tumors for the presence of PTEN. PTEN staining in tumor microarrays by FISH, immunohistochemistry and immunofluorescence show a loss of PTEN in around 10% of the tumors. We hypothesize the loss of PTEN leads to increased signaling through the IGF-1 pathway. Our results show PTEN deficient cell lines display hyper-activation of the IGF-1/Akt pathway as assayed by phosphoAKT. Additionally, Expression of exogenous PTEN in these samples decreases IGF-1/Akt signaling and shows reduced colony formation. Finally, experiments with small molecule inhibitors targeting the IGF-1 Receptor show that the presence or absence of PTEN determines the efficacy of inhibition.
Our results show that the deletion of PTEN plays an important role in tumor proliferation in Ewing tumors. Furthermore, our results suggest a subset of patients with PTEN deficient tumors will be less responsive to treatment with IGF-1 inhibitors and will need adjuvant therapy.