Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development.

The int-1 and int-2 genes were first isolated as targets for transcriptional activation by proviral insertion mutations in mammary carcinomas induced by the mouse mammary tumor virus (MMTV). Since these proto-oncogenes are not expressed at detectable levels in previously tested normal tissues from adult mice, we sought to determine whether these genes might be active during embryogenesis by examining mouse embryos and cultured teratocarcinoma cells for RNA encoded by int-1 and int-2. A single size class of int-1 RNA is present only at mid-gestation stages of development (days 8 through 13) and is also detected in testes from postpuberal mice. Four species of int-2 RNA are found in peri-implantation embryos and teratocarcinoma cells and are particularly abundant in derivatives of the primitive endodermal lineage, but int-2 RNA is not detected during mid- or late gestation or in any normal adult tissues tested. Thus, these two proto-oncogenes, activated during mammary carcinogenesis by the same mechanisms, are normally expressed at different times and places in embryonic and adult mice.