PMID- 14729621
OWN - NLM
STAT- MEDLINE
DCOM- 20040401
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 1
DP  - 2004 Jan 1
TI  - Angiogenic acceleration of Neu induced mammary tumor progression and metastasis.
PG  - 169-79
AB  - The Neu (ErbB2, HER2) member of the epidermal growth factor receptor family is 
      implicated in many human breast cancers. We have tested the importance of 
      increased angiogenic signaling in the NeuYD [mouse mammary tumor virus 
      (MMTV)-Neu(ndl)-YD5] mammary tumor model. Transgenic mice expressing vascular 
      endothelial growth factor (VEGF)(164) from the MMTV promoter were generated. 
      These mice expressed VEGF(164) RNA and protein at 20- to 40-fold higher levels 
      throughout mammary gland development but exhibited normal mammary gland 
      development and function. However, in combination with the NeuYD oncogene, 
      VEGF(164) expression resulted in increased vascularization of hyperplastic 
      mammary epithelium and dramatic acceleration of tumor appearance from 111 to 51 
      days. Gene expression profiling also indicated that the VEGF-accelerated tumors 
      were substantially more vascularized and less hypoxic. The preferential 
      vascularization of early hyperplastic portions of mammary epithelia in 
      NeuYD;MMTV-VEGF animals was associated with NeuYD RNA expression, disorganization 
      of the tight junctions, and overlapping transgenic VEGF expression. 
      NeuYD;MMTV-VEGF(164) bigenic, tumor-bearing animals resulted in an average of 10 
      tumor cell colonies/lung lodged within vascular spaces. No similar lung colonies 
      were found in control NeuYD mice with similar tumor burdens. Overall, these 
      results demonstrate the angiogenic restriction of early hyperplastic mammary 
      lesions. They also reinforce in vivo the importance of activated Neu in causing 
      disorganization of mammary luminal epithelial cell junctions and provide support 
      for an invasion-independent mechanism of metastasis.
FAU - Oshima, Robert G
AU  - Oshima RG
AD  - Oncodevelopmental Biology Program, The Burnham Institute, La Jolla, California 
      92037, USA. rgoshima@burnham.org
FAU - Lesperance, Jacqueline
AU  - Lesperance J
FAU - Munoz, Varinia
AU  - Munoz V
FAU - Hebbard, Lionel
AU  - Hebbard L
FAU - Ranscht, Barbara
AU  - Ranscht B
FAU - Sharan, Niki
AU  - Sharan N
FAU - Muller, William J
AU  - Muller WJ
FAU - Hauser, Craig A
AU  - Hauser CA
FAU - Cardiff, Robert D
AU  - Cardiff RD
LA  - eng
GR  - CA 30199/CA/NCI NIH HHS/United States
GR  - CA 74597/CA/NCI NIH HHS/United States
GR  - HD 25938/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA Primers)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Disease Progression
MH  - Mammary Neoplasms, Experimental/*blood supply/*pathology
MH  - Mammary Tumor Virus, Mouse
MH  - Mice
MH  - Mice, Transgenic
MH  - Neoplasm Metastasis
MH  - Neovascularization, Pathologic/*pathology
MH  - Polymerase Chain Reaction
MH  - Receptor, ErbB-2/*physiology
MH  - Vascular Endothelial Growth Factor A/genetics
EDAT- 2004/01/20 05:00
MHDA- 2004/04/02 05:00
CRDT- 2004/01/20 05:00
PHST- 2004/01/20 05:00 [pubmed]
PHST- 2004/04/02 05:00 [medline]
PHST- 2004/01/20 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-1944 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Jan 1;64(1):169-79. doi: 10.1158/0008-5472.can-03-1944.