Abstract 1075: STAT3 signaling in thyroid cancer

Abstract

Abstract Here, we examined the contribution of STAT3 activation in papillary thyroid carcinoma (PTC), which constitutes 80% of all thyroid malignancies. We initially examined STAT3 activation (i.e. Y705 phosphorylation) by IHC in 80 primary PTCs. Approximately 50% of the tumors expressed nuclear pSTAT3. In general, positive cancer cells were found on the edge of the tumor and in association with the stroma (also strongly pSTAT3 positive). The inner part of the tumor was generally negative, as well as all solid PTCs. Additionally, we examined human thyroid cancer derived cell lines and determined that STAT3 was phosphorylated in ∼50% and was regulated by the IL-6/gp130/JAK pathway, similarly to what has been described in breast and lung cancers. To assess STAT3's role in thyroid cancer, we evaluated the effects of STAT3 under-expression in two models: thyroid cancer derived cell lines where STAT3 levels were reduced using a short hairpin and a transgenic model of PTC lacking STAT3. We observed no significant effects on in vitro growth, migration and invasion as a consequence of reduced STAT3 levels in cancer cell lines. However, in vivo (xenografts in nude mice) the tumors with low STAT3 were significantly larger compared to control (STAT3 expressing) tumors. Similarly, in a transgenic model of PTC lacking STAT3, tumors were larger, more cellular with evidence of increased proliferation compared to the STAT3 expressing cancers. RNA expression analysis of the human xenografts suggested that tumors deficient in STAT3 have downregulated death-promoting genes. In conclusion, our data suggests that in thyroid cancer STAT3 can function as a tumor suppressor, contrary to the current dogma where STAT3 is considered to be oncogenic. We are currently determining whether STAT3's effect on tumorigenesis is dependent on “activated” or total STAT3 and hope to identify the specific molecular pathways involved. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1075. doi:10.1158/1538-7445.AM2011-1075