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Transcription factor levels in medullary thyroid carcinoma cells differentiated by Harvey ras oncogene: c-jun is
B D Nelkin1, M Borges, M Mabry
1Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Abstract:
In the TT cell line of human medullary thyroid carcinoma, the viral Harvey ras (v-rasH) oncogene induces differentiation, marked by morphological changes, diminution of growth, and increased expression of the calcitonin gene. Here, we show that the transcriptional factor c-jun is increased during v-rasH induced differentiation of TT cells both at the mRNA and functional protein levels. In contrast, nuclear proteins with binding activities related to AP2, AP3, NF1/CTF, and Sp1 were unchanged in v-rasH differentiated TT cells.
Insights
The viral Harvey ras (v-rasH) oncogene triggers differentiation in human medullary thyroid carcinoma TT cells. This process involves increased levels of the c-jun transcription factor, indicating its role in oncogene-induced cell differentiation.
Area of Science:
- Molecular Biology
- Oncology
- Cellular Differentiation
Background:
- Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of the thyroid gland.
- The TT cell line is a widely used model for studying MTC.
- Oncogenes, such as viral Harvey ras (v-rasH), can influence cell behavior, including differentiation.
Purpose of the Study:
- To investigate the molecular mechanisms underlying v-rasH-induced differentiation in TT cells.
- To identify specific transcription factors that are altered during this differentiation process.
Main Methods:
- Utilized the TT cell line derived from human medullary thyroid carcinoma.
- Induced differentiation using the viral Harvey ras (v-rasH) oncogene.
- Assessed changes in gene expression (mRNA) and protein levels of transcription factors.
Main Results:
- v-rasH oncogene induced differentiation in TT cells, characterized by morphological changes, reduced growth, and increased calcitonin gene expression.
- Significant upregulation of the transcription factor c-jun at both mRNA and functional protein levels was observed.
- Nuclear proteins associated with AP2, AP3, NF1/CTF, and Sp1 binding activities remained unchanged.
Conclusions:
- The c-jun transcription factor plays a crucial role in v-rasH-mediated differentiation of human medullary thyroid carcinoma TT cells.
- v-rasH-induced differentiation involves specific alterations in transcription factor activity, highlighting c-jun as a key player.
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