Tumorigenesis and male sterility in transgenic mice expressing a MMTV/N-ras oncogene
R Mangues1, I Seidman, A Pellicer
1Department of Pathology, New York University Medical Center, NY 10016.
Abstract:
Transgenic mice carrying the activated N-ras oncogene under the transcriptional control of the mouse mammary tumor virus (MMTV) long terminal repeat were produced. The transgene is expressed in a tissue distribution consistent with the fact that it is driven by the MMTV-LTR, and similarly to MMTV/H-ras constructs, its presence elicits tumors in Harderian, mammary and salivary glands. In addition it appears to compromise male reproductive function, which has not been described with the other ras transgenes. This finding is consistent with the existence of distinct physiological actions for each of the ras family members.
Insights
Transgenic mice with an activated N-ras oncogene developed tumors in multiple glands. This study also revealed a novel impact on male reproductive function, highlighting distinct ras family member actions.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The ras gene family plays a crucial role in cell signaling and cancer development.
- Oncogenic activation of ras genes can lead to uncontrolled cell proliferation and tumor formation.
- Previous studies utilized mouse mammary tumor virus (MMTV) long terminal repeat (LTR) constructs to drive oncogene expression.
Purpose of the Study:
- To investigate the effects of an activated N-ras oncogene expressed under the MMTV-LTR in transgenic mice.
- To characterize the tissue distribution and tumor-inducing potential of the N-ras transgene.
- To explore potential novel physiological effects of N-ras expression.
Main Methods:
- Generation of transgenic mice harboring the activated N-ras oncogene.
- Utilizing the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) for transcriptional control.
- Analysis of transgene expression patterns and tumor development in various tissues.
Main Results:
- The N-ras transgene exhibited tissue distribution consistent with MMTV-LTR regulation.
- Tumors were observed in the Harderian, mammary, and salivary glands, similar to other ras transgenes.
- A novel finding was the compromise of male reproductive function in N-ras transgenic mice.
Conclusions:
- The activated N-ras oncogene, under MMTV-LTR control, induces tumors in specific glands.
- N-ras expression has distinct physiological effects, including a previously undescribed impact on male reproductive function.
- These findings support the concept of unique physiological roles for different members of the ras gene family.
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