The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

Katrine Buch Vidén Greve, Jonas Lindgreen, Mikkel Green Terp, Steffen Schmidt, Jan Mollenhauer, Henrik Ditzel, Morten Gjerstorff

Research output: Contribution to conference without publisher/journalPosterResearch

Abstract

The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here, we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing melanoma cells was severely reduced compared to those derived from the isogenic parental cell line. Cell cycle analysis showed that SSX2 caused an accumulation of cells arrested in G1. Consistent with this, we observed a marked decrease in cells expressing the proliferation marker Ki67 and concomitantly an increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53 dependent. The growth reduction was similar in isogenic colon cancer cells with and without p53, indicating that SSX2 is able to inhibit the growth of cancer cells, even in absence of functional p53. Our results show that SSX2 acts as an inhibitor of cancer cell proliferation, possibly through replicative stress, and therefore have important implications for the use of SSX2 as a target for cancer therapy.
Translated title of the contributionCancer-kønscelle antigenet SSX2 medfører celle cyklus arrest og DNA skader i cancer celler
Original languageEnglish
Publication dateOct 2011
Number of pages1
Publication statusPublished - Oct 2011
  • Chromatin structure & function

    Katrine Buch Vidén Greve (Participant)

    5. Dec 20119. Dec 2011

    Activity: Attending an eventConference organisation or participation

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