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The int-1 proto-oncogene.

H Varmus¹, A Brown, J Papkoff

¹Department of Microbiology and Immunology, University of California, San Francisco 94143.

Princess Takamatsu Symposia

|January 1, 1986

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The int-1 proto-oncogene, activated by insertional mutations, plays a role in tumorigenesis. Its expression in embryonic development and mammary tumors suggests functional significance in cancer and cell growth.

Area of Science:

Oncogenes and Tumorigenesis
Developmental Biology
Molecular Oncology

Background:

The int-1 proto-oncogene is implicated in tumorigenesis through insertional mutagenesis.
Its expression is observed in the embryonic central nervous system, spermatogenesis, and mammary carcinomas.

Purpose of the Study:

To investigate the functional significance of the int-1 gene in oncogenesis.
To characterize the int-1 protein product and its behavior in normal development and mammary tumorigenesis.

Main Methods:

Analysis of int-1 gene expression patterns in various tissues and tumor types.
Utilizing murine leukemia virus-based vectors to assess int-1 gene function in mammary epithelial cells.
Immunoprecipitation with anti-peptide antibodies to detect int-1 protein species.

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Main Results:

Insertional mutations activating int-1 transcription are linked to tumorigenesis.
Murine leukemia virus vectors carrying int-1 altered mammary epithelial cell morphology and growth.
Multiple species of int-1 protein were identified, resulting from glycosylation and signal peptide cleavage.

Conclusions:

The int-1 proto-oncogene is functionally significant in the oncogenic process.
Further research is needed to identify the active int-1 product and its biochemical behavior.