Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid tumorigenesis is discussed in the context of the thyroid as a stable tissue, composed of differentiated cells, with a greater dissociation of control of growth from control of differentiation than is found in stem cell tissues. Experimental thyroid carcinogenesis regimes usually use mutagen exposure followed by induced growth. The normal thyroid follicle cell has a limited growth capacity, so loss of one tumour suppressor gene followed by growth-associated loss of heterozygosity would allow escape from this growth limitation, and the formation of a neoplastic clone. In man, there are two pathways of tumour formation, one through follicular adenoma to follicular carcinoma, and one to papillary carcinoma. These two pathways show differing aetiology, and differing oncogene involvement. In the follicular carcinoma pathway TSH-induced growth is relevant as it is in experimental animals. Mutagenesis is important for both papillary and follicular carcinomas. Radiation mutagenesis is of particular current importance because of the occurrence of thyroid carcinoma in children exposed to fallout from Chernobyl. The greater capacity for post-mutagen growth in children than adults is likely to explain the increased radiosensitivity of children, both to external and internal radiation.
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PMID:Thyroid tumorigenesis. 795 31

The transformation of the normal fully differentiated thyroid follicular cell to the rapidly growing undifferentiated anaplastic thyroid carcinoma cell involves a number of stages which have been defined morphologically and are now being related to various growth pathways and to molecular biological defects. The two main factors involved in this transformation are growth stimulation and mutagenesis. Growth stimulation alone, through elevated TSH, can lead to the development of thyroid tumours, usually benign, and retaining TSH dependency in some cases. Mutagens alone, if growth is suppressed, do not produce tumours, the combination of mutagens and increased growth is a potent carcinogenic regime. Non-genotoxic carcinogenesis in the thyroid involves growth, without mutagenesis the agent often causes this through affecting one component of thyroid hormone synthesis or metabolism, leading to a fall in thyroid hormone levels and a rise in TSH. Growth stimulation increases the rate of cell division, and therefore increases the chance of a mutation. Continued growth increases the change of subsequent events, in particular loss of heterozygosity in a tumour suppressor gene. The main oncogenes involved in human thyroid carcinogens are ras in the follicular tumour pathway, and ret in the papillary carcinoma pathway. p53 is involved in the progression of either papillary or follicular adenoma to an undifferentiated carcinoma. In experimental thyroid carcinogenesis, ras is again involved, with a link between the mutagenic agent used and the type of ras gene showing mutation. Analysis of the involvement of different growth factors and oncogenes in thyroid carcinogenesis suggests that genes related to the two receptors concerned with normal TSH stimulated growth, TSH receptor and the IGF1 receptor may be involved in the progression of thyroid tumours of follicular pathology. Several tyrosine kinase receptors with unknown ligands or of uncertain physiological function are linked to papillary carcinoma. The recent large increase in papillary carcinoma of the thyroid in children exposed to fallout from the Chernobyl nuclear accident underlines the importance of understanding the pathobiology of thyroid neoplasia.
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PMID:Mechanisms and pathogenesis of thyroid cancer in animals and man. 853 19

Tumours derived from the thyroid follicular epithelium represent an informative model for understanding the molecular pathogenesis of multistage tumourigenesis, which is the prevailing theory on cancer development and progression nowadays. The early stages of thyroid tumour development appear to be the consequence of the activation or 'de novo' expression of several proto-oncogenes or growth factor receptors, such as ras, ret, NTRK, met, gsp and the thyrotropin (TSH) receptor. Alterations in the expression pattern of these genes are associated with the development of differentiated neoplasms, ranging from benign toxic adenomas (gsp and TSH receptor), to follicular (ras) and papillary (ret/PTC, NTRK, met) carcinomas. They may all be considered to be early events of thyroid cell transformation and, for some, experimental evidence derived from gene transfer studies supports this hypothesis. Alterations in tumour suppressor genes (p53, Rb) are associated instead with the most aggressive and poorly differentiated forms of thyroid cancer, indicating that, in the thyroid tumourigenic process, they represent late genetic events. Specific environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. Interestingly, a high percentage of genetic lesions causing thyroid cancer originate from gene rearrangements and chromosomal translocations (ret/PTC, NTRK, Pax-8/PPARgamma) a finding which, being a rare event in most epithelial tumours, makes the molecular pathogenesis of thyroid cancer unique. The uninterrupted flow of information on the molecular genetics of thyroid nodules and cancer will broaden the correlation between genotype and phenotype and will also provide important information for the development of more accurate preoperative diagnostic tools and more efficient treatment choices for the different forms of thyroid cancer.
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PMID:Molecular pathogenesis of thyroid nodules and cancer. 1128 33