PMID- 19755514
OWN - NLM
STAT- MEDLINE
DCOM- 20100105
LR  - 20210426
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 8
IP  - 9
DP  - 2009 Sep
TI  - Tumor necrosis factor deficiency inhibits mammary tumorigenesis and a tumor 
      necrosis factor neutralizing antibody decreases mammary tumor growth in neu/erbB2 
      transgenic mice.
PG  - 2655-63
LID - 10.1158/1535-7163.MCT-09-0358 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that is 
      synthesized and secreted by cells of the immune system, as well as by certain 
      epithelia and stroma. Based on our previous studies demonstrating TNF-stimulated 
      proliferation of normal and malignant mammary epithelial cells, we hypothesized 
      that TNF might promote the growth of breast cancer in vivo. To test this, we 
      generated bigenic mice that overexpressed activated neu/erbB2 in the mammary 
      epithelium and whose TNF status was wild-type, heterozygous, or null. Mammary 
      tumorigenesis was significantly decreased in TNF-/- mice (n = 30) compared with 
      that in TNF+/+ mice (n = 27), with a palpable tumor incidence of 10.0% and 44.4%, 
      and palpable tumors/mouse of 0.10 +/- 0.06 and 0.67 +/- 0.17, respectively. 
      Tumorigenesis in the heterozygous group fell between that in the TNF+/+ and 
      TNF-/- groups, but was not significantly different from either of the homozygous 
      groups. The decreased tumor development in the TNF-/- mice was associated with a 
      decreased proliferative index in the lobular and ductal mammary epithelium. To 
      further investigate the role of TNF in breast cancer, mammary tumor-bearing mice 
      whose tumors overexpressed wild-type neu/erbB2 were treated with a 
      TNF-neutralizing antibody or a control antibody for 4 weeks (n = 20/group). 
      Mammary tumor growth was significantly inhibited in mice treated with the 
      anti-TNF antibody compared with the control antibody. Together, these data show a 
      stimulatory role for TNF in the growth of breast tumors and suggest that TNF 
      antagonists may be effective in a subset of patients with breast cancer.
FAU - Warren, Mary Ann
AU  - Warren MA
AD  - Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, 
      Buffalo, NY 14263, USA.
FAU - Shoemaker, Suzanne F
AU  - Shoemaker SF
FAU - Shealy, David J
AU  - Shealy DJ
FAU - Bshar, Wiam
AU  - Bshar W
FAU - Ip, Margot M
AU  - Ip MM
LA  - eng
GR  - CA16056/CA/NCI NIH HHS/United States
GR  - CA77656/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090915
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Carcinogens)
RN  - 0 (DNA Primers)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/*immunology
MH  - Base Sequence
MH  - Carcinogens/toxicity
MH  - DNA Primers
MH  - Female
MH  - Mammary Neoplasms, Experimental/chemically induced/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*deficiency/immunology
EDAT- 2009/09/17 06:00
MHDA- 2010/01/06 06:00
CRDT- 2009/09/17 06:00
PHST- 2009/09/17 06:00 [entrez]
PHST- 2009/09/17 06:00 [pubmed]
PHST- 2010/01/06 06:00 [medline]
AID - 1535-7163.MCT-09-0358 [pii]
AID - 10.1158/1535-7163.MCT-09-0358 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2009 Sep;8(9):2655-63. doi: 10.1158/1535-7163.MCT-09-0358. Epub 
      2009 Sep 15.