The c-ret proto-oncogene encodes a receptor tyrosine kinase whose normal function has yet to be determined. To begin to investigate the potential role of this gene in vertebrate development, we have isolated cDNA clones representing the murine c-ret gene, and have analyzed the pattern of expression during mouse embryogenesis, using northern blotting, in situ hybridization to histological sectio...

Recent genetic and functional studies have revealed striking similarities in the protein networks and molecular mechanisms altered in cancer and Parkinson's disease, as illustrated here for the converging signaling pathways of parkin and Ret [1]. These similarities may guide our thinking about potential therapies for both diseases. The proto-oncogene RET encodes a receptor tyrosine kinase that ...

The structure and function of numerous genes involved in process of carcinogenesis have been established through explosive development of molecular oncogenetics during last 15 years. Depending on the function in the cell, these genes are divided into proto-oncogenes and tumor suppressor genes. Proto-oncogenes are normal cellular genes that perform and control essential functions in the cell: gr...

PTC gene, which is derived from the rearranged form of the ret proto-oncogene, was originally discovered in human thyroid papillary carcinomas. This gene has been thought to act as a tumorigenetic factor in thyroid carcinoma, although the action of PTC oncogene products is still unknown. To study the frequency of the PTC gene present in human thyroid carcinomas, we investigated four cell lines ...

Mutations in the RET proto-oncogene are associated with the pathogenesis of medullary thyroid carcinoma (MTC). In an attempt to understand this process, we examined microdissected subpopulations from MTC and multiple metastases from these tumors. Approximately 80% of sporadic MTC's had at least one subpopulation with the RET codon 918 mutation, which is a mutation previously detected in sporadi...

Inherited cancer syndromes predispose an individual to development of specific tumors. Somatic and germline mutations in the same tumor suppressor gene, as described in Knudson's two-mutation model, are well recognized. Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndrom...

To determine effects of developmental exposure to brominated flame retardants (BFRs), weak thyroid hormone disruptors, on white matter development, white matter-specific global gene expression analysis was performed using microdissection techniques and microarrays in male rats exposed maternally to decabromodiphenyl ether (DBDE), one of the representative BFRs, at 10, 100 or 1000 ppm. Based on ...

The identification of the molecular events that drive cancer transformation is essential to the development of targeted agents that improve the clinical outcome of lung cancer. Many studies have reported genomic driver mutations in non-small-cell lung cancers (NSCLCs) over the past decade; however, the molecular pathogenesis of >40% of NSCLCs is still unknown. To identify new molecular targets ...

Medullary thyroid cancer accounts for less than 10% of all thyroid cancers. Aggressive metastatic forms of this disease however, are incurable and can cause significant symptoms including diarrhea and pain. Hereditary and some sporadic forms of the disease are characterized by a mutation of the proto-oncogene RET. This results in an abnormal growth factor receptor that, in turn, allows the mali...

The mutations of the RET proto-oncogene contributes to the development of MTC by increasing the activity of the receptor encoded by this gene. Variant T of polymorphism rs2435357 located in the enhancer of the RET gene reduces the enhancer's activity. The opposite effects of rs2435357 and the mutations causing medullary thyroid carcinoma resulted in the investigation of the status of this polym...