Fertility and sterility · 2008
Expression of insulin-like growth factors (IGFs) and IGF signaling: molecular complexity in uterine leiomyomas.
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Peng Lan, Wen Yong, Han Yulong, Wei Anran, Shi Guizhi, Mizuguchi Masashi, Lee Peng, Hernando Eva, Mittal Khush, Wei Jian-Jun
Аннотация
OBJECTIVE: To study whether dysregulation of insulin-like growth factors (IGFs) and IGF signaling are common molecular changes in symptomatic leiomyomas (fibroids) and whether IGFs are associated with large fibroids.
DESIGN: Examination of IGFs and IGF pathway genes in a large cohort of fibroids at transcriptional and translational levels. Mechanisms leading to alterations of IGFs and related genes were also analyzed.
SETTING: University clinical research laboratory.
PATIENT(S): Hysterectomies for symptomatic fibroids were collected: 180 cases from paraffin-embedded tissues and 50 cases from fresh-frozen tissues.
INTERVENTION(S): Tissue microarray and immunohistochemistry, DNA methylation analysis, reverse-transcriptase polymerase chain reaction, and Western blot.
MAIN OUTCOME MEASUREMENT(S): Transcription and translation analyses of IGF-1/2, p-AKT, p-S6K, and TSC1/2 in fibroids and matched myometrium.
RESULT(S): Insulin-like growth factors and downstream effectors were dysregulated in approximately one third of fibroids. All except for IGF-2 seemed to be abnormally regulated at translation levels. Up-regulation of IGF-2 messenger RNAs was contributed by all four alternating slicing promoters. There was a positive correlation of IGF-1 and p-AKT over-expression with fibroid size. Insulin-like growth factor 1 but not IGF-2 levels directly correlated with activation of p-AKT and p-S6K.
CONCLUSION(S): Altered expressions of IGFs and their related downstream proteins were found in one third of fibroids. Large fibroids show high levels of IGF-1 and p-AKT activity compared with small ones.
DESIGN: Examination of IGFs and IGF pathway genes in a large cohort of fibroids at transcriptional and translational levels. Mechanisms leading to alterations of IGFs and related genes were also analyzed.
SETTING: University clinical research laboratory.
PATIENT(S): Hysterectomies for symptomatic fibroids were collected: 180 cases from paraffin-embedded tissues and 50 cases from fresh-frozen tissues.
INTERVENTION(S): Tissue microarray and immunohistochemistry, DNA methylation analysis, reverse-transcriptase polymerase chain reaction, and Western blot.
MAIN OUTCOME MEASUREMENT(S): Transcription and translation analyses of IGF-1/2, p-AKT, p-S6K, and TSC1/2 in fibroids and matched myometrium.
RESULT(S): Insulin-like growth factors and downstream effectors were dysregulated in approximately one third of fibroids. All except for IGF-2 seemed to be abnormally regulated at translation levels. Up-regulation of IGF-2 messenger RNAs was contributed by all four alternating slicing promoters. There was a positive correlation of IGF-1 and p-AKT over-expression with fibroid size. Insulin-like growth factor 1 but not IGF-2 levels directly correlated with activation of p-AKT and p-S6K.
CONCLUSION(S): Altered expressions of IGFs and their related downstream proteins were found in one third of fibroids. Large fibroids show high levels of IGF-1 and p-AKT activity compared with small ones.