triiodothyronine--reverse and Breast-Neoplasms

Topics: Adenocarcinoma; Brain Neoplasms; Breast Neoplasms; Cell Proliferation; Dose-Response Relationship, Drug; Female; Glioblastoma; Humans; MCF-7 Cells; Neoplasms; Triiodothyronine, Reverse; Tumor Cells, Cultured

Thyroid hormones regulate cell proliferation, differentiation as well as apoptosis. However molecular mechanism underlying apoptosis as a result of thyroid hormone signaling is poorly understood. The antiapoptotic role of Senescence Marker Protein-30 (SMP30) has been characterized in response to varieties of stimuli as well as in knock out model. Our earlier data suggest that thyroid hormone 3, 3'5 Triiodo L Thyronine (T(3)), represses SMP30 in rat liver.. In highly metastatic MCF-7, human breast cancer cell line T3 treatment repressed SMP30 expression leading to enhanced apoptosis. Analysis by flow cytometry and other techniques revealed that overexpression and silencing of SMP30 in MCF-7 resulted in decelerated and accelerated apoptosis respectively. In order to identify the cis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected hSMP30 promoter deletion reporter vectors in MCF-7 cells. As opposed to the expected epigenetic outcome, thyroid hormone down regulated hSMP30 promoter activity despite enhanced recruitment of acetylated H3 on thyroid response elements (TREs). From the stand point of established epigenetic concept we have categorised these two TREs as negative response elements. Our attempt of siRNA mediated silencing of TRβ, reduced the fold of repression of SMP30 gene expression. In presence of thyroid hormone, Trichostatin- A (TSA), which is a Histone deacetylase (HDAC) inhibitor further inhibited SMP30 promoter activity. The above findings are in support of categorisation of both the thyroid response element as negative response elements as usually TSA should have reversed the repressions.. This is the first report of novel mechanistic insights into the remarkable downregulation of SMP30 gene expression by thyroid hormone which in turn induces apoptosis in MCF-7 human breast cancer cells. We believe that our study represents a good ground for future effort to develop new therapeutic approaches to challenge the progression of breast cancer.

Topics: Apoptosis; Binding Sites; Breast Neoplasms; Calcium-Binding Proteins; Down-Regulation; Gene Expression Regulation, Neoplastic; HEK293 Cells; Histone Acetyltransferases; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Intracellular Signaling Peptides and Proteins; Neoplasm Metastasis; Promoter Regions, Genetic; Response Elements; Selective Estrogen Receptor Modulators; Thyroid Gland; Thyroid Hormone Receptors beta; Transcription, Genetic; Transcriptional Activation; Triiodothyronine, Reverse

The relationship between the thyroid functional test in 107 malignant tumour patients' sera with Deficiency-Excessiveness Syndromes in TCM, was studied. The results revealed that there were significant differences between the FT3, FT4 in tumour and control groups (P < 0.01) as well as between the rT3, FT3/rT3 in each type of tumour and control groups (P < 0.05-0.01). There was also definite relationship between the FT3, rT3, FT3/rT3 and the degree of differentiation, rate of progression and malignancy of tumours as well. rT3 elevated and FT3 reduced in accordance with the lowering of body resistance and reinforcing of pathogenic factors. FT3, rT3, FT3/rT3 are essential factors that reflecting the wax and wane of body resistance in the cases with malignant tumours in modern medicine.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Diagnosis, Differential; Digestive System Neoplasms; Female; Humans; Lung Neoplasms; Male; Medicine, Chinese Traditional; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse