Many studies have implicated numerous
hormones,
growth factors,
cytokines and other signal transduction molecules in the pathogenesis of uterine
leiomyoma.
Estrogen and
estrogen-related genes are thought to play a key role in the growth of uterine
leiomyomas, but the molecular mechanisms are unclear. In an attempt to investigate various pathways that might be involved in
estrogen-regulated uterine
leiomyoma growth as well as to identify any novel effector genes, microarray studies comparing
estrogen-treated uterine
leiomyoma cells (UtLM) and normal myometrial cells to untreated cells were performed. Several genes were differentially expressed in
estrogen treated UtLM cells, including
insulin-like growth factor-I (
IGF-I) and others potentially involved in the
IGF-I signalling pathway, specifically genes for A-myb, a
transcription factor which promotes cell cycle progression and for MKP-1, a
dual specificity phosphatase that dephosphorylates
mitogen-activated protein kinase.
IGF-I and A-myb were up-regulated in
estrogen-treated cells while MKP-1 was down-regulated. Two other cell cycle promoting genes, c-fos and myc, were also down-regulated in
estrogen treated UtLM cells. These genes are typically up-regulated in response to
estrogen in some cells, notably breast epithelial cells, yet consistently have lower expression levels in uterine
leiomyoma tissue when compared to autologous myometrium. Our results demonstrate some novel genes that may play a role in the growth of uterine
leiomyoma, strengthen the case for involvement of the
IGF-I pathway in the response of UtLM to
estrogen and corroborate evidence that uterine smooth muscle cells respond to
estrogen with a different gene expression pattern than that seen in epithelial cells.