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Involvement of the Tpl-2/cot oncogene in MMTV tumorigenesis
K M Erny1, J Peli, J F Lambert
1Institute of Microbiology, CHUV, Lausanne, Switzerland.
Abstract:
We report for the first time a relationship between the Tpl-2/cot oncogene and Mouse Mammary Tumor Virus (MMTV) associated transformation of mammary gland cells. A sub-genomic library generated from a primary mammary gland tumor yielded a novel MMTV integration site which disrupted the Tpl-2/cot proto-oncogene between exons 7 and 8. Comparison of a cell line derived from normal mammary gland (comma-D) and a cell line established from an MMTV induced mammary tumor (GR) demonstrated similar rearrangements within Tpl-2/cot for the GR cells but not in the comma-D cells. These rearrangements in the cell line were accompanied by an increase in the level of Tpl-2/cot specific mRNA. This data suggests that Tpl-2/cot expression may be important in epithelial cell transformation or tumor progression.
Insights
This study reveals a link between the Tpl-2/cot oncogene and Mouse Mammary Tumor Virus (MMTV) in mammary gland cell transformation. MMTV integration disrupted Tpl-2/cot, increasing its mRNA and suggesting a role in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Mouse Mammary Tumor Virus (MMTV) is known to cause mammary gland tumors in mice.
- The Tpl-2/cot proto-oncogene's role in epithelial cell transformation is not fully understood.
Purpose of the Study:
- To investigate the potential relationship between MMTV and the Tpl-2/cot oncogene in mammary gland cell transformation.
- To identify novel MMTV integration sites and their impact on proto-oncogene expression.
Main Methods:
- Generated a sub-genomic library from a primary mammary gland tumor.
- Compared Tpl-2/cot gene rearrangements and mRNA levels in normal (comma-D) and MMTV-induced tumor (GR) cell lines.
- Analyzed MMTV integration sites within the Tpl-2/cot proto-oncogene.
Main Results:
- Identified a novel MMTV integration site disrupting the Tpl-2/cot proto-oncogene between exons 7 and 8.
- Observed similar Tpl-2/cot rearrangements in MMTV-induced tumor cells (GR) but not in normal cells (comma-D).
- Found increased Tpl-2/cot specific mRNA levels in GR cells with Tpl-2/cot rearrangements.
Conclusions:
- The Tpl-2/cot oncogene is implicated in MMTV-associated mammary gland cell transformation.
- MMTV integration leading to Tpl-2/cot disruption may drive tumor progression.
- Tpl-2/cot expression appears crucial for epithelial cell transformation or tumor progression in this context.