Activating transcription factor 3 gene expression suggests that tissue stress plays a role in leiomyoma development

Objective: To determine whether expression of the stress response gene ATF3 and related members of activator protein complex-1, cJun and cFos, were altered in leiomyoma compared with myometrium, and whether this difference might correlate with leiomyoma size or race. Design: Laboratory study. Setting: University hospital. Patient(s): Fifteen women undergoing hysterectomy for symptomatic leiomyoma. Intervention(s): Tissue procurement, RNA isolation, reverse-transcriptase polymerase chain reaction, real-time reverse-transcriptase polymerase (RT-PCR) chain reaction, immunohistochemistry, Western blot. Main Outcome Measure(s): Expression of mRNA and protein in leiomyoma and patient-matched myometrium. Result(s): mRNA transcripts of ATF3 were decreased in leiomyoma compared with matched myometrium by both RT-PCR and real-time RT-PCR. The decrease was greater than fivefold in a majority of samples. The reduction seen in ATF3 mRNA expression did not show a correlation with race and leiomyoma size. Surprisingly, immunohistochemistry and Western blot analysis demonstrated an elevation of ATF3 protein expression by a mean of 2.9-fold. Transcripts of related AP-1 genes, cJun and cFos, were significantly decreased by a mean of -29.57 for cJun and -23.78 for cFos, but there was no significant change in protein expression of the two transcription factors. Conclusions: Alterations in ATF3 gene expression resemble the response to mechanical and ischemic stress reported in other tissues. Results suggested that ATF3 protein expression was increased in leiomyoma, and may reflect increased tissue stress.