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

34 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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T2 - molecular complexity in uterine leiomyomas

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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N2 - 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.

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 - leiomyomas

KW - promoter

KW - tissue microarray

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