The effects of SV40 transformation on the levels of messenger RNA of C-ERBA BETA 1, C-ERBA ALPHA 1, and C-ERBA ALPHA 2 receptors in fibroblasts from patients of kindred S with generalized resistance to thyroid hormone / by Uyen K. Nguyen.
| Author/creator | Nguyen, Uyen K. author. |
| Other author | Klann, Richard C., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1994. |
| Description | vi, 48 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | At the physiological level, cancer can be defined as aberrant modifications of the normal cell signal transduction pathways. Thyroid hormones, triiodothyronine and thyroxine are chemical messengers that are produced and secreted by the thyroid gland. They have an important role in modulating various processes involving normal cellular growth and development all throughout life. At the transcriptional level, thyroid hormones act cooperatively with their physiological receptors (c-erbA proto-oncogenes) to selectively regulate gene expression of many genes. Since both thyroid hormone and its receptors have been implicated in the process of neoplastic transformation in rodent models, it was important to examine, in a human cell transformation model, the transcriptional regulation of these receptors. Fibroblasts from patients with Generalized Resistance to Thyroid Hormone were transfected with an SV40 plasmid construct coding for a protein, the SV40 large T antigen, which served to transform the cells and was detectable by immunofluorescence. Subsequent mRNA quantitation of the c-erbA thyroid hormone receptors was accomplished by reverse transcription-competitive polymerase chain reaction methodology. In order to obtain correct assessment of mRNA levels of these thyroid hormone receptors (THRs) under neoplastic conditions, certain cell properties characteristic of in vitro neoplastic transformation were confirmed. Fibroblasts of each genotype displayed nuclear expression of the SV40 large T antigen by immunofluorescence, accompanied by morphological transformation and increased in vitro growth rate. In contrast, there were no changes in the absolute levels of any of the THR mRNAs examined. In addition, T3 depletion or replacement was without effect on THR mRNA levels in cells from the homozygous mutant. These differences from the rodent fibroblast models may reflect incomplete transformation of these cells by large T antigen, or a fundamental difference in the involvement of thyroid hormone in transformation of human cells. |
| General note | Submitted to the faculty of the Department of Biology. |
| General note | Advisor: Richard C. Klann |
| Dissertation note | M.S. East Carolina University 1994 |
| Bibliography note | Includes bibliographical references (leaves 45-48). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
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