Restoration of C/EBPα in dedifferentiated liposarcoma induces G2/M cell cycle arrest and apoptosis Journal Article

Authors: Wu, Y. V.; Okada, T.; Decarolis, P.; Socci, N.; O'Connor, R.; Geha, R. C.; Somberg, C. J.; Antonescu, C.; Singer, S.
Article Title: Restoration of C/EBPα in dedifferentiated liposarcoma induces G2/M cell cycle arrest and apoptosis
Abstract: Well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) represent the most common biological group of liposarcoma, and there is a pressing need to develop targeted therapies for patients with advanced disease. To identify potential therapeutic targets, we sought to identify differences in the adipogenic pathways between DDLS, WDLS, and normal adipose tissue. In a microarray analysis of DDLS (n = 84), WDLS (n = 79), and normal fat (n = 23), C/EBPα, a transcription factor involved in cell cycle regulation and differentiation, was underexpressed in DDLS when compared to both WDLS and normal fat (15.2- and 27.8-fold, respectively). In normal adipose-derived stem cells, C/EBPα expression was strongly induced when cells were cultured in differentiation media, but in three DDLS cell lines, this induction was nearly absent. We restored C/EBPα expression in one of the cell lines (DDLS8817) by transfection of an inducible C/EBPα expression vector. Inducing C/EBPα expression reduced proliferation and caused cells to accumulate in G2/M. Under differentiation conditions, the cell proliferation was reduced further, and 66% of the DDLS cells containing the inducible C/EBPα expression vector underwent apoptosis as demonstrated by annexin V staining. These cells in differentiation conditions expressed early adipocyte-specific mRNAs such as LPL and FABP4, but they failed to accumulate intracellular lipid droplets, a characteristic of mature adipocytes. These results demonstrate that loss of C/EBPα is an important factor in suppressing apoptosis and maintaining the dedifferentiated state in DDLS. Restoring C/EBPα may be a useful therapeutic approach for DDLS. © 2011 Wiley Periodicals, Inc.
Keywords: controlled study; human tissue; protein expression; human cell; comparative study; cell proliferation; apoptosis; culture medium; cancer cell culture; genetic transfection; microarray analysis; cell cycle arrest; cell cycle g2 phase; cell cycle m phase; cell cycle regulation; bioaccumulation; liposarcoma; adipose tissue; expression vector; cell dedifferentiation; adipogenesis; dedifferentiated liposarcoma; adipose derived stem cell; ccaat enhancer binding protein alpha; well differentiated liposarcoma
Journal Title: Genes Chromosomes and Cancer
Volume: 51
Issue: 4
ISSN: 1045-2257
Publisher: Wiley Periodicals, Inc  
Date Published: 2012-04-01
Start Page: 313
End Page: 327
Language: English
DOI: 10.1002/gcc.21917
PROVIDER: scopus
PUBMED: 22170698
PMCID: PMC3375024
Notes: --- - "Export Date: 1 March 2012" - "CODEN: GCCAE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Rula Christine Geha
    10 Geha
  2. Yuhsin Victoria Wu
    6 Wu
  3. Cristina R Antonescu
    612 Antonescu
  4. Samuel Singer
    233 Singer
  5. Tomoyo Okada
    14 Okada
  6. Nicholas D Socci
    188 Socci