Understanding the many facets of RET/PTC oncogene activity in thyroid carcinoma: Transformation, inflammation, and antigenicity
RET/PTC oncogenes are highly prevalent in papillary thyroid carcinoma, an indolent and well-differentiated cancer. Previous in vitro and in vivo studies have established that RET/PTC oncoproteins induce both pro-tumorigenic and pro-inflammatory programs when expressed in the context of follicular thyroid cells. The tumorigenic properties of RET/PTC are attributed to RAS-mediated activation of RAF/MEK/ERK and PI3K/AKT pathways. Although oncogenic forms of RAS and BRAF are associated with papillary thyroid carcinoma that may progress to more aggressive types such as poorly-differentiated follicular or anaplastic carcinoma, RET/PTC oncogenes are only associated with papillary thyroid carcinoma development. Furthermore RET/PTCs are strongly associated with the autoimmune disorder Hashimoto's thyroiditis, while oncogenic forms of RAS and BRAF are not. Taking into consideration the divergent phenotypes of these follicular cell-derived cancers, the potential for uncoupling the RET/PTC-mediated pro-inflammatory activity from the tumorigenic property was investigated. Herein, biochemical and in vitro approaches were utilized to analyze the mechanisms that render RET/PTC-expressing cells both oncogenic, immunostimulatory, and antigenic.
Wixted, Josephine Fox, "Understanding the many facets of RET/PTC oncogene activity in thyroid carcinoma: Transformation, inflammation, and antigenicity" (2012). ETD Collection for Thomas Jefferson University. AAI3489728.