Estrogen plays an essential role in gro
wth and progression of human breast cancer. Particularly, local estrogen biosynthesis must be important for etiology of this disease. Since estrogen signaling is also activated by the gro
wth factor-mediating phosphorylation signal, breast cancer strongly depends upon local cancer microenvironment. Then, to analyze the estrogen-related cancer microenvironment of individual breast cancer tissues,
we established ne
w reporter cell system,
which
was stably transfected GFP reporter DNA inserted estrogen response element in MCF-7 cells. It enables to analyze ER
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-activation activity of stromal cells in individual cancer patients. We found that ER
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-activation activity and effect of aromatase inhibitors varied among the individual cases but correlated
with histological grade, indicating that the ability of stromal cells in adjacent to cancer cells must be unique and important. Furthermore, these ER
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-activation signals in the microenvironment stimulate follo
wing intracellular estrogen-signal transduction in cancer cells. Our estrogen-responsive microarray analysis, real-time RT-PCR, and immunohistochemical technique revealed several ne
w target genes
which correlate
with prognosis of breast cancer and play an important role in cancer development. For example,
we found that transcription factor EGR3
was the bona fide target gene for ER
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> and might involve
with invasive property in breast cancer. Furthermore, the expression of another do
wnstream gene HDAC6 significantly correlated
with survival of breast cancer patients. In vitro study revealed that the HDAC6 caused the deacetylation of
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-tubulin in cytosol and induced cell motility in ER
![](http://<font color=)
www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-positive breast cancer cells. We hope that these approaches could provide not only ne
w clues for elucidation of the mechanisms of estrogen-dependent gro
wth and development of breast cancer, but also clinical benefits to patients by assessment of individual response to hormonal therapy.