PMID- 1359541 OWN - NLM STAT- MEDLINE DCOM- 19921223 LR - 20220316 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 89 IP - 22 DP - 1992 Nov 15 TI - Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. PG - 10578-82 AB - Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have been implicated in the development of aggressive human breast cancer. To directly assess the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying unactivated neu under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were established. By contrast to the rapid tumor progression observed in several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the mammary epithelium resulted in the development of focal mammary tumors after long latency. The majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and protein. Overexpression of neu in the mammary tumors was also associated with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. These observations suggest that overexpression of the unactivated neu protein can induce metastatic disease after long latency. FAU - Guy, C T AU - Guy CT AD - Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada. FAU - Webster, M A AU - Webster MA FAU - Schaller, M AU - Schaller M FAU - Parsons, T J AU - Parsons TJ FAU - Cardiff, R D AU - Cardiff RD FAU - Muller, W J AU - Muller WJ LA - eng GR - R01-CA S4285/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM GS - ERBB2 GS - c-erbB2 GS - neu MH - Animals MH - Epithelium/pathology/physiology MH - Female MH - Kinetics MH - Male MH - Mammary Glands, Animal/pathology/*physiology MH - Mammary Neoplasms, Experimental/*genetics/*pathology MH - Mice MH - Mice, Transgenic MH - Neoplasm Metastasis/*genetics/pathology MH - Proto-Oncogene Proteins/*genetics MH - *Proto-Oncogenes MH - Receptor, ErbB-2 PMC - PMC50384 EDAT- 1992/11/15 00:00 MHDA- 1992/11/15 00:01 PMCR- 1993/05/15 CRDT- 1992/11/15 00:00 PHST- 1992/11/15 00:00 [pubmed] PHST- 1992/11/15 00:01 [medline] PHST- 1992/11/15 00:00 [entrez] PHST- 1993/05/15 00:00 [pmc-release] AID - 10.1073/pnas.89.22.10578 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82. doi: 10.1073/pnas.89.22.10578.