Functional mammary gland development and oncogene-induced tumor formation are not affected by the absence of the retinoblastoma gene

results in impaired mammary gland development and neoplasia. We investigate d the consequences of the absence of pRb in mammary epithelial cells during normal development and in mice that express an oncogene in the mammary epi thelium. Since pRb-deficiency results in embryonic lethality, we transplant ed pRb-null mammary anlagen into wild hosts. pRb-deficient mammary epitheli a were capable of functional differentiation in term animals and they regen erated a differentiated gland even after multiple pregnancies. In serial tr ansplantations no significant differences were found in outgrowth of pRb-de ficient and wild type epithelia indicating that the absence of pRb does not lead to transformation. Likewise the effect of a TGF beta1 transgene was n ot altered in the absence of pRb. The susceptibility of mammary epithelium to form tumors was assessed in three different models. No differences in tu mor incidence were found between wild type and Rb +/- WAP-int3, MMTV-PyMT t ransgenic and Brcal(-/-) epithelia. These results demonstrate that the abse nce of pRb does not affect normal mammary gland development and tumorigenes is in three different mouse models investigated and suggest that loss of mo re than one member of the pRb pathway is required to induce mammary tumors.