Characterization and Consequences of Estrogen Receptor Exon Five Deletion.
Annual rept. 1 Sep 94-31 Jun 95,
MOUNT SINAI MEDICAL CENTER OF THE CITY OF NEW YORK
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Normal breast growth and development is dependent on estrogen signaling through the estrogen receptor ER. In addition to its normal function, many studies have conclusively demonstrated the involvement of estrogen as a mitogen in breast tumors. The recent identification of estrogen receptor mRNA splice isoforms has lead to the hypothesis that de-regulation of ER pre-mRNA splicing contributes to the etiology of breast cancer. Data in this report begin to clarify the function of a non- DNA binding estrogen receptor isoform ERA3 in both tumor and normal breast biology. Currently, our studies suggest that normal mammary epithelium contains significantly higher levels of ERA3 mRNA than we have observed in breast tumors or tumor cell lines. In addition, MCF-7 cells a breast tumor cell line which have been stably transfected to overexpress ERA3, gain a morphologically more differentiated phenotype, partially characterized by their ability to form domes with a hollow lumen, as well as their decreased growth rate in response to estrogen. These results have lead us to propose that ERA3 functions to attenuate the responsiveness of normal mammary epithelium to the growth stimulatory effects of estrogen. Consequently, the loss of ERA3 expression in breast tumors may enhance the mitogenic effects of estrogen, thereby contributing to disease progression.
- Medicine and Medical Research