Endocrine Abstracts

Most cellular actions of the steroid and thyroid hormones, vitamins A and D, and other small lipophilic molecules are mediated through binding to nuclear receptors, which act as ligand-inducible transcription factors by recruiting coactivators and corepressors. Steroid receptors bind as homodimers to hormone-response elements (HREs) in target genes, while non-steroid receptors generally bind DNA as heterodimers with the retinoid X receptor (RXR). Our understanding of nuclear r...

Nuclear receptors such as the thyroid hormone receptors (TR α and β) or vitamin D receptors (VDR) regulate gene expression by binding to DNA as heterodimers with the retinoid X receptor (RXR). Their effects on transcription are mediated by the recruitment of coregulators (coactivators and corepressors). The C-terminal AF-2 receptor domains are required for coactivators recruitment. The RXR ligand (9-cis-RA) cooperates with the ligand of its partner receptor to...

Lymphangiogenesis is a very important event in breast cancer development and VEGF-C and D factors play an essential role in this process. Tumoral invasion of lymphatic vessels facilitates metastasis formation and is a bad pronostic marker in this pathology. Although the thyroid hormone receptors (TRs) are ubiquitously expressed in normal tissues, inactivation and mutations of the TRβ gene are usual events in breast cancer, suggesting that the native receptors could act as...

The known functions of the thyroid hormones in the liver have expanded from their well-known roles in regulating metabolism to also participate in liver regeneration, senescence and hepatocarcinogenesis. The transcription factors STAT3 and NF-κB play a key role in liver homeostasis, in the response to infection and inflammation and in hepatocarcinoma development. Interleukin 6 (IL-6) and Tumour Necrosis α (TNFα) are the best-known cytokines responsible for hepat...

Reduced expression or activity of the thyroid hormone receptors (TRs) are common events in cancer, suggesting that these receptors could act as tumor suppressors. We have previously shown that TRβ expression in SK-hep1 hepatocarcinoma cells (SK-TRβ cells), reduces tumor growth and strikingly inhibits invasion, extravasation, and metastasis formation in nude mice. These effects could be related to a decreased expression in these cells of prometastatic genes, such as C...

Fibrosis represents a major health concern and presently has no successful treatment. Chronic liver fibrosis leads to portal hypertension, cirrhosis, hepatocellular carcinoma and liver failure. Transforming growth factor β (TGFβ), the main profibrogenic factor, mediates its actions mainly through activation of Smad transcription factors. We have previously observed a cross-talk between the thyroid hormone receptors (TRs) and the TGFβ pathway by which the thyroid...

Transforming growth factor beta (TGFβ), which plays a key role in cancer and fibrotic disorders, mediates its actions mainly through activation of Smad transcription factors, which bind to Smad Binding Elements (SBEs) in target genes. We have previously observed that the thyroid hormone T3 blocks transactivation of SBE-containing reporter plasmids by TGFβ, and represses transcription of endogenous TGFβ target genes. We have now analysed the thyroid ho...

Transforming growth factor β (TGFβ) signals through activation of Smad transcription factors, which bind to Smad binding elements (SBEs) in target genes. TGFβ can promote cancer cell proliferation and invasion, and plays a key role in the pathogenesis of scleroderma and other fibrotic disorders. We have previously shown that the thyroid hormone receptors (TRs) can block tumor growth and invasion. We now have analyzed the possibility that TRs could antagonize TGF...

Nuclear corepressor 1 (NCoR) associates with nuclear receptors and other transcription factors leading to transcriptional repression. Genomic studies have shown the presence of inactivating mutations of the NCoR gene in human tumours and we have found that NCoR depletion with siRNA in hepatocarcinoma SK-hep1 cells enhances invasion, tumour growth and metastasis in nude mice, while expression of the thyroid hormone receptor β (TRβ) increases NCoR levels, repr...