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

174 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

Fingerprint

Protein Phosphatase 2
Breast Neoplasms
Growth
Oncogene Proteins
Proteins
Heterografts
Messenger RNA
Nude Mice
Cell Movement

Keywords

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

Cite this

Côme, C., Laine, A., Chanrion, M., Edgren, H., Mattila, E., Lin, X., ... 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
Côme, Christophe ; Laine, Anni ; Chanrion, Maïa ; Edgren, Henrik ; Mattila, Elina ; Lin, Xiaoling ; Jonkers, Jos ; Ivaska, Johanna ; Isola, Jorma ; Darbon, Jean-Marie ; Kallioniemi, Olli ; Thézenas, Simon ; Westermarck, Jukka. / CIP2A Is Associated with Human Breast Cancer Aggressivity. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 16. pp. 5092-5100.
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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.",
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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, vol. 15, no. 16, pp. 5092-5100. https://doi.org/10.1158/1078-0432.CCR-08-3283

CIP2A Is Associated with Human Breast Cancer Aggressivity. / Côme, Christophe; Laine, Anni; Chanrion, Maïa; Edgren, Henrik; Mattila, Elina; Lin, Xiaoling; Jonkers, Jos; Ivaska, Johanna; Isola, Jorma; Darbon, Jean-Marie; Kallioniemi, Olli; Thézenas, Simon; Westermarck, Jukka.

In: Clinical Cancer Research, Vol. 15, No. 16, 2009, p. 5092-5100.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - CIP2A Is Associated with Human Breast Cancer Aggressivity

AU - Côme, Christophe

AU - Laine, Anni

AU - Chanrion, Maïa

AU - Edgren, Henrik

AU - Mattila, Elina

AU - Lin, Xiaoling

AU - Jonkers, Jos

AU - Ivaska, Johanna

AU - Isola, Jorma

AU - Darbon, Jean-Marie

AU - Kallioniemi, Olli

AU - Thézenas, Simon

AU - Westermarck, Jukka

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - breast cancer

KW - CIP2A

KW - gene expression

KW - mRNA

KW - mRNA gene transcription

U2 - 10.1158/1078-0432.CCR-08-3283

DO - 10.1158/1078-0432.CCR-08-3283

M3 - Article

VL - 15

SP - 5092

EP - 5100

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 16

ER -

Côme C, Laine A, Chanrion M, Edgren H, Mattila E, Lin X et al. CIP2A Is Associated with Human Breast Cancer Aggressivity. Clinical Cancer Research. 2009;15(16):5092-5100. https://doi.org/10.1158/1078-0432.CCR-08-3283