PMID- 8622899
OWN - NLM
STAT- MEDLINE
DCOM- 19960618
LR  - 20081121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 12
IP  - 8
DP  - 1996 Apr 18
TI  - NDF/heregulin induces persistence of terminal end buds and adenocarcinomas in the 
      mammary glands of transgenic mice.
PG  - 1781-8
AB  - Neu differentiation factor (NDF), a member of the neuregulin family of ligands of 
      erbB receptors, induces both differentiative and mitogenic effects on cultured 
      human mammary epithelial cells. Since members of the epidermal growth factor 
      receptor family, including Neu/erbB2, have been implicated in mammary carcinoma, 
      we wished to know whether a potential ligand of this family, NDF, could induce 
      such effects in the mammary gland in vivo. We therefore targeted expression of 
      NDF to the mammary gland of transgenic mice using the mouse mammary tumor virus 
      (MMTV) promoter in a fusion construct. There was a clear, but subtle effect on 
      development of the adult virgin gland of female transgenic animals. Terminal end 
      bud structures (TEBs), which normally disappear from the mammary gland at the age 
      of approximately 8 weeks in wild type mice, persist in glands of virgin MMTV-NDF 
      transgenic females, suggesting that NDF inhibits signals that normally lead to 
      the terminal differentiation of these structures. Further, female mice, bred 
      continuously to maximize expression of the transgene in the mammary gland, 
      develop mammary adenocarcinomas at a median age of 12 months. Since these tumors 
      arise in a solitary fashion, we infer that NDF is necessary, but not sufficient 
      for their formation. In order to explore the signal transduction pathways 
      potentially activated by NDF, we examined expression of the receptors erbB2, 
      erbB3 and erbB4 in mammary epithelial cells established from an NDF-induced 
      tumor. All three receptors were expressed, though only the erbB3 receptor was 
      phosphorylated, suggesting that overexpression of NDF might operate through this 
      receptor. Additionally, about 50% of MMTV-NDF transgenic mice developed Harderian 
      (lachrymal) gland hyperplasia, a benign tumor that does not progress to frank 
      malignancy.
FAU - Krane, I M
AU  - Krane IM
AD  - Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Leder, P
AU  - Leder P
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Glycoproteins)
RN  - 0 (Neuregulins)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Adenocarcinoma/*genetics/pathology
MH  - Animals
MH  - Base Sequence
MH  - Epithelium
MH  - Female
MH  - Gene Expression Regulation
MH  - Glycoproteins/*genetics
MH  - Harderian Gland/pathology
MH  - Mammary Glands, Animal/*pathology/ultrastructure
MH  - Mammary Neoplasms, Animal/*genetics/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Neuregulins
MH  - Promoter Regions, Genetic
MH  - Receptors, Thyroid Hormone/genetics
MH  - Recombinant Fusion Proteins/genetics
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
EDAT- 1996/04/18 00:00
MHDA- 1996/04/18 00:01
CRDT- 1996/04/18 00:00
PHST- 1996/04/18 00:00 [pubmed]
PHST- 1996/04/18 00:01 [medline]
PHST- 1996/04/18 00:00 [entrez]
PST - ppublish
SO  - Oncogene. 1996 Apr 18;12(8):1781-8.