PMID- 11304693
OWN - NLM
STAT- MEDLINE
DCOM- 20010524
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 92
IP  - 4
DP  - 2001 May 15
TI  - Impairment of mammary lobular development induced by expression of TGFbeta1 under 
      the control of WAP promoter does not suppress tumorigenesis in MMTV-infected 
      transgenic mice.
PG  - 568-76
AB  - It has previously been shown that transgenic female mice expressing TGFbeta1 
      under control of regulatory elements of the whey-acidic protein (WAP) gene were 
      unable to lactate. This was due to the increased apoptosis of the cells committed 
      to the lobular-lactogenic phenotype. Our goal was to determine whether the 
      expression of WAP-TGFbeta1 transgene could inhibit MMTV (mouse mammary tumor 
      virus) tumorigenic activity in the mammary gland. It is well known that the 
      infection with this virus produces focal hyperplastic secretory nodules (HANs) 
      and, some variants can also induce ductal pregnancy-dependent lesions (plaques). 
      In either case, MMTV infection leads ultimately to the appearance of malignant 
      mammary tumors. The results shown herein demonstrate that TGFbeta1 expression in 
      the secretory mammary epithelium does not suppress mammary tumorigenesis in MMTV 
      infected mice. Although MMTV infected WAP-TGFbeta1 transgenic females displayed a 
      strong impairment of lobule-alveolar development, carcinogenesis induced by any 
      of the four MMTV variants used herein proceeded unabated. WAP-TGFbeta1 tumors 
      that showed a strong expression at the WAP promoter, appeared later and grew more 
      slowly than their wild-type counterparts. Transgenic females also had a lower 
      incidence of HANs and plaques. Our study suggests that the epithelial target 
      cells for tumorigenic mutations are probably progenitor cells that are not 
      susceptible to the apoptotic effect of TGFbeta1. Alternatively, their daughters 
      cells that display the secretory phenotype and could be more involved in the 
      formation of premalignant lesions continue to die due to the expression of the 
      transgene.
FAU - Buggiano, V
AU  - Buggiano V
AD  - ILEX-CONICET, Division de Medicina Experimental, Instituto de Investigaciones 
      Hematologicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
FAU - Schere-Levy, C
AU  - Schere-Levy C
FAU - Abe, K
AU  - Abe K
FAU - Vanzulli, S
AU  - Vanzulli S
FAU - Piazzon, I
AU  - Piazzon I
FAU - Smith, G H
AU  - Smith GH
FAU - Kordon, E C
AU  - Kordon EC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Milk Proteins)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (whey acidic proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Breast/*metabolism
MH  - Epithelium/metabolism
MH  - Female
MH  - Mammary Neoplasms, Animal/metabolism/virology
MH  - Mammary Neoplasms, Experimental/metabolism/virology
MH  - Mammary Tumor Virus, Mouse/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Milk Proteins/*genetics
MH  - Phenotype
MH  - *Promoter Regions, Genetic
MH  - Stem Cells/metabolism
MH  - Transforming Growth Factor beta/*biosynthesis
MH  - Transforming Growth Factor beta1
MH  - Transgenes
EDAT- 2001/04/17 10:00
MHDA- 2001/05/26 10:01
CRDT- 2001/04/17 10:00
PHST- 2001/04/17 10:00 [pubmed]
PHST- 2001/05/26 10:01 [medline]
PHST- 2001/04/17 10:00 [entrez]
AID - 10.1002/ijc.1232 [pii]
AID - 10.1002/ijc.1232 [doi]
PST - ppublish
SO  - Int J Cancer. 2001 May 15;92(4):568-76. doi: 10.1002/ijc.1232.