Estrogen receptor expression in sporadic vestibular schwannomas

Abstract

Hypothesis: We hypothesize that vestibular schwannomas (VSs) exhibit up-regulation of estrogen receptor (ER) at the protein level compared with control great auricular nerve (GAN).

Background: It has been reported in the literature that VS occur more commonly in women and tend to be larger and more vascular in women, and growth rate can accelerate during pregnancy. The literature contains widely divergent results on ER expression in VS, however, varying from no detectable levels to detection of ER in all samples.

Methods: Sixteen sporadic VS specimens were immediately snap-frozen after microsurgical excision and analyzed for phosphorylated and total levels of ERα with Western blot analysis. ERα expression levels were normalized to actin; then, relative expression to GAN was determined.

Results: All VS specimens exhibited expression of both phosphorylated and total ERα. Total ERα expression in VS is equivalent to or slightly up-regulated compared with GAN. VS specimens exhibited more pronounced up-regulation of phosphorylated (i.e., activated) levels of ERα compared with GAN.

Conclusion: We have demonstrated that ERα expression in VS is equivalent to GAN. The phosphorylated form of the receptor is up-regulated compared with GAN, however, indicating a higher level of ERα activation in sporadic VS compared with normal nerve. Further investigation into antiestrogen therapy for VS is warranted.

Figure 1

Expression of (A) total ERα and (C) phosphorylated (Ser118) ERα. (B) and (D) depict actin for total and phosphorylated ERα, respectively. From left to right, lanes are control nerve (GAN), VS specimen 40, 41, 42 and 43, followed by an empty lane. MCF-7, an immortalized breast cancer cell line, serves as positive control in the far right lane.

Figure 2

Band intensities for total ERα were quantified using the public domain Image J program (developed at the NIH). To correct for protein loading, band intensities were normalized to actin, and then expressed as Relative Intensity to control nerve (GAN). GAN is arbitrarily designated as “one.”

Figure 3

Band intensities of phosphorylated ERα, normalized to actin and expressed as Relative Intensity to control GAN. GAN is arbitrarily designated as “one.”