Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 877-888 |
| Number of pages | 12 |
| Journal | Neoplasia |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2010 |
| MoE publication type | A1 Journal article-refereed |
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Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2. / Rantala, Juha K. (Corresponding Author); Edgren, Henrik; Lehtinen, Laura; Wolf, Maija; Kleivi, Kristine; Vollan, H.K.; Aaltola, Anna-Riina; Laasola, Petra; Kilpinen, Sami; Saviranta, Petri; Iljin, Kristiina; Kallioniemi, Olli (Corresponding Author).
In: Neoplasia, Vol. 12, No. 11, 2010, p. 877-888.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2
AU - Rantala, Juha K.
AU - Edgren, Henrik
AU - Lehtinen, Laura
AU - Wolf, Maija
AU - Kleivi, Kristine
AU - Vollan, H.K.
AU - Aaltola, Anna-Riina
AU - Laasola, Petra
AU - Kilpinen, Sami
AU - Saviranta, Petri
AU - Iljin, Kristiina
AU - Kallioniemi, Olli
PY - 2010
Y1 - 2010
N2 - Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication, and possibly through polyploid intermediate states. To identify molecular processes contributing to development of aneuploidy, we used a cell spot microarray technique to identify genes inducing polyploidy and/or allowing maintenance of polyploid cell growth in breast cancer cells. Of 5760 human genes screened, 177 were found to induce severe DNA content alterations on prolonged transient silencing. Association with response to DNA damage stimulus and DNA repair was found to be the most enriched cellular processes among the candidate genes. Functional validation analysis of these genes highlighted GINS2 as the highest ranking candidate inducing polyploidy, accumulation of endogenous DNA damage, and impairing cell proliferation on inhibition. The cell growth inhibition and induction of polyploidy by suppression of GINS2 was verified in a panel of breast cancer cell lines. Bioinformatic analysis of published gene expression and DNA copy number studies of clinical breast tumors suggested GINS2 to be associated with the aggressive characteristics of a subgroup of breast cancers in vivo. In addition, nuclear GINS2 protein levels distinguished actively proliferating cancer cells suggesting potential use of GINS2 staining as a biomarker of cell proliferation as well as a potential therapeutic target.
AB - Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication, and possibly through polyploid intermediate states. To identify molecular processes contributing to development of aneuploidy, we used a cell spot microarray technique to identify genes inducing polyploidy and/or allowing maintenance of polyploid cell growth in breast cancer cells. Of 5760 human genes screened, 177 were found to induce severe DNA content alterations on prolonged transient silencing. Association with response to DNA damage stimulus and DNA repair was found to be the most enriched cellular processes among the candidate genes. Functional validation analysis of these genes highlighted GINS2 as the highest ranking candidate inducing polyploidy, accumulation of endogenous DNA damage, and impairing cell proliferation on inhibition. The cell growth inhibition and induction of polyploidy by suppression of GINS2 was verified in a panel of breast cancer cell lines. Bioinformatic analysis of published gene expression and DNA copy number studies of clinical breast tumors suggested GINS2 to be associated with the aggressive characteristics of a subgroup of breast cancers in vivo. In addition, nuclear GINS2 protein levels distinguished actively proliferating cancer cells suggesting potential use of GINS2 staining as a biomarker of cell proliferation as well as a potential therapeutic target.
U2 - 10.1593/neo.10548
DO - 10.1593/neo.10548
M3 - Article
VL - 12
SP - 877
EP - 888
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 11
ER -