Comparative analysis of AKT and the related biomarkers in uterine leiomyomas with MED12, HMGA2, and FH mutations

Jia Xie, Julianne Ubango, Yanli Ban, Debabrata Chakravarti, J. Julie Kim, Jian Jun Wei*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Uterine leiomyomas (ULM) are histologically and molecularly heterogeneous and clinically they grow at vastly different rates. Several driver gene mutations have been identified in ULM, including MED12 mutations, HMGA2 overexpression, and biallelic FH inactivation. ULM with different driver mutant genes may use different molecular pathways, but currently no clear correlation between gene mutations and growth related pathways has been established. To better define this relationship, we collected ULM with MED12 (n = 25), HMGA2 (n = 15), and FH (n = 27) mutations and examined the sex steroid hormone, cell cycle, and AKT pathway genes by immunohistochemistry. While ER and PR were highly expressed in all types of ULM, FH ULM showed lower ER expression and higher PR expression. HMGA2 tumors had significantly higher levels of AKT signaling and mitogenic activity than other ULM types. HMGA2 activated AKT signaling through upregulation of IGF2BP2. Silencing HMGA2 in ULM cells resulted in downregulation of AKT and upregulation of p16 and p21, which eventually led to cell senescence. HMGA2 overexpression in ULM is not only related to tumor development but also plays a role in controlling cellular proliferation through the AKT pathway.

Original languageEnglish (US)
Pages (from-to)485-494
Number of pages10
JournalGenes Chromosomes and Cancer
Volume57
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • AKT pathway
  • FH
  • HMGA2
  • MED12
  • cell cycle
  • leiomyoma

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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