Nucleotide Sequence and Expression In Vitro of cDNA Derived from mRNA of <i>int</i>-1, a Provirally Activated Mouse Mammary Oncogene

The proto-oncogene int-1 is activated by adjacent insertions of proviral DNA in mouse mammary tumor virus-induced tumors and has transforming activity in certain mammary epithelial cell lines. The gene is normally expressed in the central nervous system of mid-gestational embryos and in the adult testis. We raised antibodies against synthetic int-1 peptides and used these to identify protein products of the gene in cells transfected or infected with retroviral vectors expressing int-1. Four protein species of 36,000, 38,000, 40,000, and 42,000 Mr were immunoprecipitated by antibodies against two different int-1 peptides and were not present in control cells. Partial degradation with V8 protease showed the four species to be structurally related to each other and to int-1 polypeptide synthesized in vitro. Treatment of the cells with tunicamycin prevented the appearance of all but the 36,000-Mr species, suggesting that the slower-migrating forms are glycosylated derivatives. The unglycosylated 36,000-Mr species migrated faster in polyacrylamide gels than the in vitro translation product of int-1 and has probably undergone cleavage of an amino-terminal signal peptide.

Section: Methodsmentioning

confidence: 99%

Identification of Protein Products Encoded by the Proto-Oncogene int-1

Brown

Papkoff

Fung

et al. 1987

“…The int-i proto-oncogene is one of a series of genes that is activated in mouse mammary tumors by insertion of proviral DNA (19,19a,20). The gene encodes a cysteine-rich protein with a typical signal peptide (7,27). During its synthesis and transport, the int-i protein is glycosylated and enters the secretory pathway, suggesting that the protein is released from cells (3,21).…”

mentioning

confidence: 99%

Transient Expression of the Proto-Oncogene int-1 during Differentiation of P19 Embryonal Carcinoma Cells

Schuuring

Deemter

Roelink

et al. 1989

In mouse embryos, the int-1 proto-oncogene is transiently expressed in areas of the developing neural system. Retinoic acid-treated P19 embryonal carcinoma cells have often been used as an in vitro model for the molecular basis of neural development. We shown here that int-1 is transiently expressed in differentiated P19 cells. The time course and retinoic acid dose dependence of int-1 expression suggest that the gene is specifically expressed during early neural differentiation. P19 cells may be a useful model to assist in the study, at the cellular level, of the role of int-1 in neural development.

“…The Wnt-1 gene encodes a 44-kDa cysteine-rich secreted glycoprotein (4,13,37,38) that is tightly associated with the extracellular matrix and/or the cell surface (3,38). Normal expression of the mouse Wnt-1 gene has been shown to be spatially and temporally regulated during development.…”

mentioning

confidence: 99%

Differential Regulation of the Wnt Gene Family during Pregnancy and Lactation Suggests a Role in Postnatal Development of the Mammary Gland

Gavin

McMahon

1992

The mouse Wnt family comprises at least 10 members sharing substantial amino acid identity with the secreted glycoprotein Wnt-1/int-1. Two of these, Wnt-1 and Wnt-3, are implicated in mouse mammary tumor virus-associated adenocarcinomas, although neither member is normally expressed in the mammary gland. These results suggest the presence of active cellular pathways which mediate the action of Wnt-1 and Wnt-3 signals. An understanding of the normal role of these signalling pathways is clearly necessary to comprehend the involvement of Wnt-1 and Wnt-3 in mammary tumorigenesis. We demonstrate here that five Wnt family members are expressed and differentially regulated in the normal mouse mammary gland. In addition, some of these genes are also expressed in both Wnt-1-responsive and nonresponsive mammary epithelial cell lines. We propose that Wnt-mediated signalling is involved in normal regulation of mammary development and that inappropriate expression of Wnt-1, Wnt-3, and possibly other family members can interfere with these signalling pathways.