PMID- 19012101
OWN - NLM
STAT- MEDLINE
DCOM- 20090130
LR  - 20151119
IS  - 1473-0766 (Electronic)
IS  - 0951-3590 (Linking)
VI  - 24
IP  - 10
DP  - 2008 Oct
TI  - Effects of estradiol and progestogens on tumor-necrosis factor-alpha-induced 
      changes of biochemical markers for breast cancer growth and metastasis.
PG  - 576-9
LID - 10.1080/09513590802288267 [doi]
AB  - BACKGROUND: Epidemiological data suggest an enhanced breast cancer risk during 
      estrogen/progestogen therapy as compared to estrogen monotherapy in 
      postmenopausal women. The underlying mechanism, however, still remains unknown. 
      Estrogens are known to be mitogenic agents for benign and cancerous breast 
      epithelial cells whereas the role of progestogens is unclear. Tumor-associated 
      macrophages play a crucial role in tumor growth and metastasis due to the 
      synthesis of various cytokines such as tumor necrosis factor-alpha (TNF-alpha), 
      which can stimulate the synthesis of proliferative and angiogenic factors in 
      tumor cells. In an in vitro model we investigated the influence of estradiol and 
      estradiol/progestogens combinations on the changes of TNF-alpha- induced markers. 
      METHODS: MCF-7 cells, a human estrogen- and progesterone-receptor-positive human 
      breast cancer cell line, were used for the experiments. Estradiol (E(2)), at a 
      concentration of 0.1 nM, and the progestogens progesterone (P), norethisterone 
      (NET) and medroxyprogesterone acetate (MPA), each at concentrations of 0.01 to 1 
      microM, were tested alone and in combination. The cells were incubated for 4 days 
      and the markers monocyte chemoattractant protein-1 (MCP-1), vascular endothelial 
      growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured in the 
      supernatant by enzyme-linked immunosorbent assay. RESULTS: E(2) in combination 
      with TNF-alpha elicited significant increases in MCP-1 and VEGF concentrations 
      compared with TNF-alpha alone. For the progestogens alone an increase of MCP-1 
      was observed for NET, whereas MPA induced a decrease. An increase of VEGF was 
      observed for all progestogens, the effect being greatest for MPA. No changes were 
      found for MMP-9. In combinations with E(2), the E(2)-induced increase of MCP-1 
      was reduced by NET and MPA and the increase of VEGF was diminished by P and NET, 
      but not by MPA. The E(2)-induced decrease of MMP-9 was not antagonized by P and 
      NET, but completely abolished by MPA. CONCLUSION: Our results indicate that E(2) 
      may have a stimulating effect on pre-existing tumor growth and metastasis. This 
      effect seems to be influenced by progestogens in a different manner. Thus the 
      choice of progestogen addition to estrogen therapy may be important, especially 
      since different effects can occur in the case of pre-existing tumor cells.
FAU - Seeger, Harald
AU  - Seeger H
AD  - Section of Endocrinology and Menopause, University Women's Hospital, Tuebingen, 
      Germany.
FAU - Wallwiener, Diethelm
AU  - Wallwiener D
FAU - Mueck, Alfred O
AU  - Mueck AO
LA  - eng
PT  - Journal Article
PL  - England
TA  - Gynecol Endocrinol
JT  - Gynecological endocrinology : the official journal of the International Society 
      of Gynecological Endocrinology
JID - 8807913
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Progestins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 4TI98Z838E (Estradiol)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Biomarkers/*metabolism
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Chemokine CCL2/analysis/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Humans
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Medroxyprogesterone Acetate/pharmacology
MH  - Neoplasm Metastasis
MH  - Progestins/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2008/11/18 09:00
MHDA- 2009/01/31 09:00
CRDT- 2008/11/18 09:00
PHST- 2008/11/18 09:00 [pubmed]
PHST- 2009/01/31 09:00 [medline]
PHST- 2008/11/18 09:00 [entrez]
AID - 905586157 [pii]
AID - 10.1080/09513590802288267 [doi]
PST - ppublish
SO  - Gynecol Endocrinol. 2008 Oct;24(10):576-9. doi: 10.1080/09513590802288267.