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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 2009

Fingerprint

Leiomyoma
Somatomedins
Myometrium
DNA Methylation
Reverse Transcriptase Polymerase Chain Reaction
Hysterectomy
Paraffin
Genes

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Expression of insulin-like growth factors (IGFs) and IGF signaling : molecular complexity in uterine leiomyomas. / Peng, Lan; Wen, Yong; Han, Yulong; Wei, Anran; Shi, Guizhi; Mizuguchi, Masashi; Lee, Peng; Hernando, Eva; Mittal, Khush; Wei, Jian Jun.

In: Fertility and Sterility, Vol. 91, No. 6, 06.2009, p. 2664-2675.

Research output: Contribution to journalArticle

Peng, L, Wen, Y, Han, Y, Wei, A, Shi, G, Mizuguchi, M, Lee, P, Hernando, E, Mittal, K & Wei, JJ 2009, 'Expression of insulin-like growth factors (IGFs) and IGF signaling: molecular complexity in uterine leiomyomas', Fertility and Sterility, vol. 91, no. 6, pp. 2664-2675. https://doi.org/10.1016/j.fertnstert.2007.10.083
Peng, Lan ; Wen, Yong ; Han, Yulong ; Wei, Anran ; Shi, Guizhi ; Mizuguchi, Masashi ; Lee, Peng ; Hernando, Eva ; Mittal, Khush ; Wei, Jian Jun. / Expression of insulin-like growth factors (IGFs) and IGF signaling : molecular complexity in uterine leiomyomas. In: Fertility and Sterility. 2009 ; Vol. 91, No. 6. pp. 2664-2675.
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AU - Peng, Lan

AU - Wen, Yong

AU - Han, Yulong

AU - Wei, Anran

AU - Shi, Guizhi

AU - Mizuguchi, Masashi

AU - Lee, Peng

AU - Hernando, Eva

AU - Mittal, Khush

AU - Wei, Jian Jun

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AB - 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.

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KW - promoter

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