Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 67, Issue 1, Pages 51-60Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1010662905549
Keywords
angiogenesis; hypoxia; MCF-7; VEGF
Categories
Funding
- NCI NIH HHS [R01 CA75285] Funding Source: Medline
Ask authors/readers for more resources
Previous work from this laboratory demonstrated that MCF-7 breast carcinoma cells grown in nude mice contained minimal hypoxia but that tamoxifen treatment of these tumors resulted in increased hypoxia (Evans S. et al., Cancer Research, 1997). These findings led to studies exploring the link between estrogen signaling and tumor oxygenation and determining the role of VEGF in this process. The stimulation of estrogen-dependent MCF-7 breast carcinoma cells in vitro with beta -estradiol resulted in a two-fold induction of VEGF mRNA and 1.3-2-fold increase in protein, similar to what was observed when these cells were exposed to 0.1% oxygen. Furthermore, the two stimuli given together had an additive effect on (increasing) VEGF expression, suggesting that the combination of hypoxia and estrogen may be important in upregulating VEGF in some breast cancers. Estrogen-independent MCF-7-5C cells, developed by growing MCF-7 cells in long-term culture in estrogen-free media, were also studied. Using EF5, a fluorinated 2-nitroimidazole which localizes to hypoxic cells, MCF-7-5C tumors grown in nude mice were found to contain lower pO(2) levels and more hypoxic regions than similarly grown MCF-7 tumors. We tested the hypothesis that this might be the result of defective expression of VEGF in MCF-7-5C cells in response to beta -estradiol and/or hypoxia. However, MCF-7-5C and MCF-7 cells showed a similar induction of VEGF in vitro in response to either beta -estradiol or hypoxia. Therefore, although these two cell lines grown as tumors have substantial differences in the presence and patterns of hypoxia, this could not be explained by a difference in VEGF induction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available