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Expression of Steroid Receptor Coactivators in Cultured Cells From Paired Myometrial and Fibroid Tissues

Peter J. Fuller, MD, PhD

Prince Henry's Institute of Medical Research and Monash University Department of Medicine; Department of Obstetrics and Gynaecology, Monash University, Centre for Women's Health Research, Clayton, Victoria, Australia

Caroline E. Gargett, PhD

Prince Henry's Institute of Medical Research and Monash University Department of Medicine; Department of Obstetrics and Gynaecology, Monash University, Centre for Women's Health Research, Clayton, Victoria, Australia; Monash University, Department of Obstetrics and Gynaecology, Centre for Women's Health Research, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria, 3168 Australia caroline.gargett{at}med.monash.edu.au

Objectives: Fibroid tumor growth in the myometrium appears to be regulated by estrogens but the role of estrogen receptor (ER) coregulators, such as the steroid receptor coactivator (SRC) family members, in fibroid growth is currently unknown. The aims of this study were to compare the expression of the SRC-1, SRC-2, and SRC-3 coactivators between fibroids and normal myometrium in pure populations of cultured smooth muscle cells (SMC) and microvascular endothelial cells (MEC), and also between both cell types, and to identify any relationship between the SRC expression profiles and the known ER status of the SMC and MEC samples examined in this study.

Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) coupled with Southern blot analysis was used to derive a semiquantitative estimate of the relative levels of SRC-1, SRC-2, and SRC-3 expression in pure populations of SMC (>98% -smooth muscle actin [SMA]⁺) and MEc (>99% CD31⁺) isolated and cultured from eight samples of paired human myometrial and fibroid tissue.

Results: The mean levels of SRC-1, SRC-2, and SRC-3 were each similar in normal myometrium compared to fibroids for SMC and also for MEC. However, SRC-1, SRC-2, and SRC-3 levels were each significantly higher in SMC compared to MEC from both myometrial and fibroid samples, although for SRC-3 there was a trend for higher levels in myometrial samples that did not reach significance. While all SMC samples expressed ER and high coactivator levels, there does not appear to be a relationship between coactivator expression levels and the presence or absence of ER in MEC samples.

Conclusion: Coactivators may be more important in ER-mediated growth of SMC than for MEC. Although the SRC family members are likely to play a role in the response of fibroid SMC to estrogen, via ER, changes in their levels do not appear to contribute to the increased sensitivity of fibroid SMC to estrogen.

Key Words: SRC-1 • SCR2/TIF2 • SRC-3/AIB1 • estrogen recepton • myometrium • fibroids • microvascular endothelial cells • smooth muscle cells

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