PMID- 16536875
OWN - NLM
STAT- MEDLINE
DCOM- 20060509
LR  - 20181113
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 6
DP  - 2006 Mar 14
TI  - Transgenic mice with mammary gland targeted expression of human cortactin do not 
      develop (pre-malignant) breast tumors: studies in MMTV-cortactin and 
      MMTV-cortactin/-cyclin D1 bitransgenic mice.
PG  - 58
AB  - BACKGROUND: In human breast cancers, amplification of chromosome 11q13 correlates 
      with lymph node metastasis and increased mortality. To date, two genes located 
      within this amplicon, CCND1 and EMS1, were considered to act as oncogenes, 
      because overexpression of both proteins, respectively cyclin D1 and cortactin, 
      correlated well with 11q13 amplification. Cyclin D1 is involved in cell cycle 
      regulation and the F-actin-binding protein cortactin in cytoskeletal dynamics and 
      cell migration. To study the role of cortactin in mammary gland tumorigenesis, we 
      examined mouse mammary tumor virus (MMTV)-cortactin transgenic mice and 
      MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice. METHODS: MMTV-cortactin 
      transgenic mice were generated and intercrossed with previously described 
      MMTV-cyclin D1 transgenic mice. Immunohistochemical, Northern and Western blot 
      analyses were performed to study the expression of human transgene cortactin 
      during mammary gland development and in mammary tumors. For tumor incidence 
      studies, forced-bred, multiparous mice were used to enhance transgene expression 
      in the mammary gland. Microscopical examination was performed using haematoxylin 
      and eosin staining. RESULTS: Mammary gland tumors arose stochastically (incidence 
      21%) with a mean age of onset at 100 weeks. This incidence, however, did not 
      exceed that of aged-matched control FVB/N mice (38%), which unexpectedly, also 
      developed spontaneous mammary gland tumors. We mimicked 11q13 amplification by 
      generating MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice but did not observe 
      any synergistic effect of cortactin on cyclin D1-induced mammary hyperplasias or 
      carcinomas, nor development of distant metastasis. CONCLUSION: From this study, 
      we conclude that development of (pre-malignant) breast tumors in either wild type 
      or MMTV-cyclin D1 mice was not augmented due to mammary gland targeted 
      overexpression of human cortactin.
FAU - van Rossum, Agnes G S H
AU  - van Rossum AG
AD  - Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300 
      RC Leiden, The Netherlands. a.van.rossum@nin.knaw.nl
FAU - van Bragt, Maaike P A
AU  - van Bragt MP
FAU - Schuuring-Scholtes, Ellen
AU  - Schuuring-Scholtes E
FAU - van der Ploeg, Jan C M
AU  - van der Ploeg JC
FAU - van Krieken, Johan H J M
AU  - van Krieken JH
FAU - Kluin, Philip M
AU  - Kluin PM
FAU - Schuuring, Ed
AU  - Schuuring E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060314
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (CTTN protein, human)
RN  - 0 (Cortactin)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Animals
MH  - Cortactin/analysis/*genetics/physiology
MH  - Cyclin D1/genetics
MH  - Female
MH  - Gene Expression
MH  - Gene Targeting
MH  - Humans
MH  - Mammary Glands, Animal/anatomy & histology/metabolism/pathology
MH  - Mammary Neoplasms, Experimental/*genetics/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Precancerous Conditions/genetics/pathology
PMC - PMC1450299
EDAT- 2006/03/16 09:00
MHDA- 2006/05/10 09:00
PMCR- 2006/03/14
CRDT- 2006/03/16 09:00
PHST- 2005/12/06 00:00 [received]
PHST- 2006/03/14 00:00 [accepted]
PHST- 2006/03/16 09:00 [pubmed]
PHST- 2006/05/10 09:00 [medline]
PHST- 2006/03/16 09:00 [entrez]
PHST- 2006/03/14 00:00 [pmc-release]
AID - 1471-2407-6-58 [pii]
AID - 10.1186/1471-2407-6-58 [doi]
PST - epublish
SO  - BMC Cancer. 2006 Mar 14;6:58. doi: 10.1186/1471-2407-6-58.