Thyroid Development and Its Disorders: Genetics and Molecular Mechanisms

Stazione Zoologica Anton Dohrn, University of Naples Federico II, 80121 Naples, Italy.
Endocrine Reviews (Impact Factor: 21.06). 11/2004; 25(5):722-46. DOI: 10.1210/er.2003-0028
Source: PubMed

ABSTRACT Thyroid gland organogenesis results in an organ the shape, size, and position of which are largely conserved among adult individuals of the same species, thus suggesting that genetic factors must be involved in controlling these parameters. In humans, the organogenesis of the thyroid gland is often disturbed, leading to a variety of conditions, such as agenesis, ectopy, and hypoplasia, which are collectively called thyroid dysgenesis (TD). The molecular mechanisms leading to TD are largely unknown. Studies in murine models and in a few patients with dysgenesis revealed that mutations in regulatory genes expressed in the developing thyroid are responsible for this condition, thus showing that TD can be a genetic and inheritable disease. These studies open the way to a novel working hypothesis on the molecular and genetic basis of this frequent human condition and render the thyroid an important model in the understanding of molecular mechanisms regulating the size, shape, and position of organs.

13 Reads
  • Source
    • "In such cases, the clinical presentation varies depending on the location of ectopic thyroid tissue [3]. Ectopic thyroid may develop the same diseases that affect the normal orthotopic thyroid gland [4]. However, primary carcinomas arising from ectopic thyroid tissue are very rare. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid carcinoma arising in an extrathyroid area is a rare entity. We report a case of anaplastic carcinoma in the submandibular region occurring in a 70-year-old woman. The location of the mass along with no evidence of primary tumor at the orthotopic thyroid gland posed a diagnostic dilemma: was this an ectopic thyroid carcinoma or rather a case of occult differentiated thyroid carcinoma metastasis that transformed to anaplastic carcinoma? Based on the histopathological findings we concluded that the tumor arised in ectopic thyroid tissue. Although the mass was completely resected, the patient died 10 months after diagnosis due to pulmonary metastases. Conclusively, the possibility of ectopic thyroid tissue, with or without disease, should be considered in cases of a mass in the submandibular region. Copyright © 2015. Published by Elsevier Ltd.
    International Journal of Surgery Case Reports 02/2015; 8. DOI:10.1016/j.ijscr.2015.02.015
  • Source
    • "The mesenchymal tissue is involved in thyroid development being that it releases Pro-epidermal growth factor (EGF) and basic fibroblast growth factor-2 (FGF-2), promoting cell proliferation and repressing differentiation (76, 77). Estrogens play a pivotal role in this context by inducing the production of EGF and other TFs, such as TGF-α (5). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent discoveries highlight the emerging role of estrogens in the initiation and progression of different malignancies through their interaction with stem cell (SC) compartment. Estrogens play a relevant role especially for those tumors bearing a gender disparity in incidence and aggressiveness, as occurs for most thyroid diseases. Although several experimental lines suggest that estrogens promote thyroid cell proliferation and invasion, their precise contribution in SC compartment still remains unclear. This review underlines the interplay between hormones and thyroid function, which could help to complete the puzzle of gender discrepancy in thyroid malignancies. Defining the association between estrogen receptors' status and signaling pathways by which estrogens exert their effects on thyroid cells is a potential tool that provides important insights in pathogenetic mechanisms of thyroid tumors.
    Frontiers in Endocrinology 07/2014; 5:124. DOI:10.3389/fendo.2014.00124
  • Source
    • "Knockout mice lacking PAX8 have a smaller thyroid, with normal calcitonin-producing parafollicular C cells but no follicular cells; thus, they suffer from severe hypothyroidism [7]. Congenital hypothyroidism is caused by several genetic defects, and among these there are mutations of the PAX8 gene [8]. In addition to hypothyroidism, PAX8 plays a role in the progression of follicular thyroid carcinomas and adenomas [9] and is overexpressed in the majority of gliomas, Wilms tumors and well-differentiated pancreatic neuroendocrine tumors [10-12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: PAX8 is a member of the paired box (Pax) multigene family of transcription factors, which are involved in the developmental and tissue-specific control of the expression of several genes in both vertebrates and invertebrates. Previously, several studies reported that PAX8 is expressed at high levels in specific types of tumors. In particular, PAX8 has been recently reported to be conspicuously expressed in human ovarian cancer, but the functional role of PAX8 in the carcinogenesis of this type of tumor has not been addressed. In this study, we investigated the contribution of PAX8 in ovarian cancer progression. Stable PAX8 depleted ovarian cancer cells were generated using short hairpin RNA (shRNA) constructs. PAX8 mRNA and protein were detected by RT-PCR, immunoblot and immunofluorescence. Cell proliferation, motility and invasion potential of PAX8 silenced cells were analyzed by means of growth curves, wound healing and Matrigel assays. In addition, PAX8 knockdown and control cells were injected into nude mice for xenograft tumorigenicity assays. Finally, qPCR was used to detect the expression levels of EMT markers in PAX8-overexpressing and control cells. Here, we show that PAX8 plays a critical role in the migration, invasion and tumorigenic ability of ovarian cancer cells. Our results show that RNA interference-mediated knockdown of PAX8 expression in SKOV-3 ovarian cancer cells produces a significant reduction of cell proliferation, migration ability and invasion activity compared with control parental SKOV-3 cells. Moreover, PAX8 silencing strongly suppresses anchorage-independent growth in vitro. Notably, tumorigenesis in vivo in a nude mouse xenograft model is also significantly inhibited. Overall, our results indicate that PAX8 plays an important role in the tumorigenic phenotype of ovarian cancer cells and identifies PAX8 as a potential new target for the treatment of ovarian cancer.
    BMC Cancer 04/2014; 14(1):292. DOI:10.1186/1471-2407-14-292 · 3.36 Impact Factor
Show more


13 Reads