Reflections

  Significance Overview   RET/PTCs are a group of oncogenic fusion proteins derived from the proto-oncogene c-RET, structurally related to a family of receptor tyrosine kinases (1-3). RET/PTCs result from joining the carboxy-terminus of fusion partners with the amino-terminus of c-RET, leading to constitutively active kinase. Of the 11 different fusion genes reported, RET/PTC1 or RP1 and RET/PTC3 or RP3 are the most prevalent (1). In the case of RP3, the amino terminus is derived from the androgen receptor-associated protein, ARA-70 (Fig. 1) (4). RP3 drives three different pathways that strongly influence biological properties of the tumor. First, the constitutively active c-terminal RET kinase domain activates RAS/BRAF/MEK/ERK, PI3K/AKT, p38MAPK, and JNK pathways leading to thyrocyte transformation (5). Second, kinase activity leads to precocious phosphorylation of RP3 itself and other intracellular proteins that provide tumor-specific targets for the adaptive immu...

  RET/PTC3 Oncogene's Inflammatory Properties and Hashimoto's Thyroiditis   Various components of the ability to fight of infection in a host are collectively termed as immune system. Swelling, redness, pain and heat at the site of infection are hallmark of the active immune system and are defined as inflammation. Generally, more robust the inflammatory reaction is, the better it is for the host to clear the infection. Cancers are different as they are said to be actively causing the development of inflammation. The reason is that increased blood flow to the site of cancer brings more and more nutrients and other mediators which contradictorily help expand the cancer growth. We however believe that to be inaccurate, at best reflecting certain cancers only. We investigate papillary thyroid carcinoma (PTC) which is one of the most prevalent endocrine tumor known, accounting for about 85% of the thyroid malignancies. The incidence of thyroid cancers is on the rise too, in USA and...