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Aromatase activity in human ovarian cancer
N J MacLusky1, R Voit, J S Lazo
1Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
Abstract:
Eighty-four tumor samples from 70 women with primary ovarian cancer were assayed for cytosol estrogen (ERc) and progestin (PRc) receptor concentrations and aromatase activity. In addition, 22 of the tumors were studied for their response to the aromatase inhibitor, 4-OH-androstenedione, in a soft agar clonogenic cell assay system. Although aromatase activity was detected in almost all of the primary tumors, this enzyme was barely detectable in the majority of metastatic tumor samples. There was no significant correlation between aromatase activity and either the ERc or PRc content of the tumors, or tumor grade. Of 12 tumors grown successfully in the soft agar culture system, only 1 showed a substantial (greater than 50%) reduction in colony-forming efficiency after exposure to the aromatase inhibitor. These results suggest that local estrogen biosynthesis probably does not play an important role in the majority of epithelial ovarian tumors. However, there may be a small subset of estrogen receptor-positive tumors in which aromatase could provide a local growth stimulus.
Insights
Local estrogen production via aromatase is unlikely to drive most ovarian cancers. However, a small group of estrogen receptor-positive tumors might be influenced by this pathway.
Area of Science:
- Oncology
- Endocrinology
- Biochemistry
Background:
- Estrogen biosynthesis, particularly through aromatase, is implicated in hormone-dependent cancers.
- The role of local estrogen production in epithelial ovarian cancer (EOC) remains incompletely understood.
Purpose of the Study:
- To investigate the activity of aromatase and its correlation with estrogen (ERc) and progestin (PRc) receptors in primary and metastatic ovarian tumors.
- To assess the in vitro efficacy of the aromatase inhibitor 4-OH-androstenedione on ovarian tumor cells.
Main Methods:
- Assay of cytosol estrogen (ERc) and progestin (PRc) receptor concentrations and aromatase activity in 84 primary ovarian tumor samples.
- Soft agar clonogenic cell assay of 22 tumors treated with the aromatase inhibitor 4-OH-androstenedione.
Main Results:
- Aromatase activity was prevalent in primary tumors but minimal in metastatic samples.
- No significant correlation was found between aromatase activity and ERc/PRc levels or tumor grade.
- Only one of 12 tumors in soft agar showed a significant response to the aromatase inhibitor.
Conclusions:
- Local estrogen biosynthesis through aromatase is unlikely to be a major factor in the majority of epithelial ovarian cancers.
- A potential role for aromatase in promoting growth may exist in a small subset of estrogen receptor-positive ovarian tumors.