Expression of insulin-like growth factors (IGFs) and IGF signaling: molecular complexity in uterine leiomyomas

Lan Peng, Yong Wen, Yulong Han, Anran Wei, Guizhi Shi, Masashi Mizuguchi, Peng Lee, Eva Hernando, Khush Mittal, Jian Jun Wei*

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2664-2675
Number of pages12
JournalFertility and Sterility
Volume91
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • IGF pathway
  • IGF-1
  • IGF-2
  • leiomyomas
  • promoter
  • tissue microarray

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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