Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo

E Sinn , W Muller , P Pattengale

Cell +

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May 22, 1987

View abstract on PubMed

Summary

Transgenic mice with v-Ha-ras or c-myc genes developed cell growth issues and tumors. Combining these genes synergistically accelerated tumor formation, indicating further genetic events are needed for malignancy.

Area Of Science

Oncology
Genetics
Molecular Biology

Background

The v-Ha-ras and c-myc oncogenes are frequently implicated in cancer development.
The mouse mammary tumor virus (MMTV) promoter/enhancer is a common tool for driving oncogene expression in transgenic mice, particularly in mammary tissues.

Purpose Of The Study

To investigate the roles of v-Ha-ras and c-myc oncogenes in tumorigenesis using transgenic mouse models.
To determine the synergistic effects of co-expressed v-Ha-ras and c-myc on tumor development and progression.

Main Methods

Generation of transgenic mouse lines expressing either v-Ha-ras or c-myc under the MMTV promoter.
Cross-breeding of MMTV/v-Ha-ras and MMTV/c-myc transgenic mice to create hybrid offspring.
Histopathological analysis of tumors arising in transgenic and hybrid mice.

Main Results

MMTV/v-Ha-ras transgenic mice exhibited benign Harderian gland hyperplasia and focal malignancies in mammary, salivary, and lymphoid tissues.
Hybrid mice co-expressing MMTV/v-Ha-ras and MMTV/c-myc showed a significant and synergistic acceleration of tumor formation.
Tumorigenesis in these models, even with activated oncogenes, appeared to require additional stochastic somatic events for full malignant progression.

Conclusions

Co-expression of v-Ha-ras and c-myc oncogenes synergistically promotes tumor development.
Tumorigenesis driven by these oncogenes is a multi-step process, necessitating further genetic alterations for malignancy.
Transgenic mouse models provide valuable insights into the complex genetic events underlying cancer initiation and progression.

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