CIP2A Is Associated with Human Breast Cancer Aggressivity

Christophe Côme, Anni Laine, Maïa Chanrion, Henrik Edgren, Elina Mattila, Xiaoling Lin, Jos Jonkers, Johanna Ivaska, Jorma Isola, Jean-Marie Darbon, Olli Kallioniemi, Simon Thézenas, Jukka Westermarck

Research output: Contribution to journalArticleScientificpeer-review

183 Citations (Scopus)

Abstract

Purpose: To investigate the clinical relevance of the recently characterized human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) in human breast cancer.

Experimental Design: CIP2A expression (mRNA and protein) was measured in three different sets of human mammary tumors and compared with clinicopathologic variables. The functional role of CIP2A in breast cancer cells was evaluated by small interfering RNA–mediated depletion of the protein followed by an analysis of cell proliferation, migration, anchorage-independent growth, and xenograft growth.

Results: CIP2A mRNA is overexpressed (n = 159) and correlates with higher Scarff-Bloom-Richardson grades (n = 251) in samples from two independent human breast cancer patients. CIP2A protein was found to be overexpressed in 39% of 33 human breast cancer samples. Furthermore, CIP2A mRNA expression positively correlated with lymph node positivity of the patients and with the expression of proliferation markers and p53 mutations in the tumor samples. Moreover, CIP2A protein expression was induced in breast cancer mouse models presenting mammary gland–specific depletion of p53 and either BRCA1 or BRCA2. Functionally, CIP2A depletion was shown to inhibit the expression of its target protein c-Myc. Loss of CIP2A also inhibited anchorage-independent growth in breast cancer cells. Finally, CIP2A was shown to support MDA-MB-231 xenograft growth in nude mice.

Conclusions: Our data show that CIP2A is associated with clinical aggressivity in human breast cancer and promotes the malignant growth of breast cancer cells. Thus, these results validate the role of CIP2A as a clinically relevant human oncoprotein and warrant further investigation of CIP2A as a therapeutic target in breast cancer treatment.
Original languageEnglish
Pages (from-to)5092-5100
JournalClinical Cancer Research
Volume15
Issue number16
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Keywords

  • breast cancer
  • CIP2A
  • gene expression
  • mRNA
  • mRNA gene transcription

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  • Cite this

    Côme, C., Laine, A., Chanrion, M., Edgren, H., Mattila, E., Lin, X., Jonkers, J., Ivaska, J., Isola, J., Darbon, J-M., Kallioniemi, O., Thézenas, S., & Westermarck, J. (2009). CIP2A Is Associated with Human Breast Cancer Aggressivity. Clinical Cancer Research, 15(16), 5092-5100. https://doi.org/10.1158/1078-0432.CCR-08-3283