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

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.

• Authors: Lan Peng, Yong Wen, Yulong Han, Anran Wei, Guizhi Shi, Masashi Mizuguchi, Peng Lee, Eva Hernando, Khush Mittal, Jian-Jun Wei
• Journal: Fertility and sterility (Fertil Steril) Vol. 91 Issue 6 Pg. 2664-75 (Jun 2009) ISSN: 1556-5653 [Electronic] United States
• PMID: 18439583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Somatomedins

Topics

• Cohort Studies
• DNA Primers
• Exons (genetics)
• Female
• Humans
• Hysterectomy
• Leiomyoma (genetics, physiopathology, surgery)
• Oligonucleotide Array Sequence Analysis
• Protein Biosynthesis
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Somatomedins (genetics, physiology)
• Transcription, Genetic
• Uterine Neoplasms (genetics, physiopathology, surgery)