Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome

E. K A Millar, J. L. Dean, C. M. McNeil, S. A. O'Toole, S. M. Henshall, T. Tran, J. Lin, A. Quong, C. E S Comstock, A. Witkiewicz, E. A. Musgrove, H. Rui, L. Lemarchand, V. W. Setiawan, C. A. Haiman, K. E. Knudsen, R. L. Sutherland, E. S. Knudsen

Research output: Contribution to journalArticle

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Abstract

Aberrant expression of cyclin D1 protein is a common feature of breast cancer. However, the CCND1 gene encodes two gene products, cyclin D1a and cyclin D1b, which have discrete mechanisms of regulation and impact on cell behavior. A polymorphism at nucleotide 870 in the CCND1 gene, rs603965, influences the relative production of the encoded proteins and can impart increased risk for tumor development. Here, the impact of both the G/A870 polymorphism and cyclin D1b protein production on breast cancer risk, disease phenotype and patient outcome was analysed. In a large multiethnic case-control study, the G/A870 polymorphism conferred no significant risk for breast cancer overall or by stage or estrogen receptor (ER) status. However, the cyclin D1b protein was found to be upregulated in breast cancer, independent of cyclin D1a levels, and exhibited heterogeneous levels in breast cancer specimens. High cyclin D1a expression inversely correlated with the Ki67 proliferation marker and was not associated with clinical outcome. In contrast, elevated cyclin D1b expression was independently associated with adverse outcomes, including recurrence, distant metastasis and decreased survival. Interestingly, cyclin D1b was particularly associated with poor outcome in the context of ER-negative breast cancer. Thus, specific cyclin D1 isoforms are associated with discrete forms of breast cancer and high cyclin D1b protein levels hold prognostic potential.

Original languageEnglish (US)
Pages (from-to)1812-1820
Number of pages9
JournalOncogene
Volume28
Issue number15
DOIs
StatePublished - Apr 16 2009

Fingerprint

Cyclins
Breast Neoplasms
Proteins
Cyclin D1
Estrogen Receptors
Genes
Case-Control Studies
Protein Isoforms
Nucleotides
Neoplasm Metastasis
Phenotype
Recurrence
Survival

Keywords

  • Breast cancer
  • Cyclin D1b
  • Estrogen receptor
  • Polymorphism
  • Prognosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Millar, E. K. A., Dean, J. L., McNeil, C. M., O'Toole, S. A., Henshall, S. M., Tran, T., ... Knudsen, E. S. (2009). Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. Oncogene, 28(15), 1812-1820. https://doi.org/10.1038/onc.2009.13

Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. / Millar, E. K A; Dean, J. L.; McNeil, C. M.; O'Toole, S. A.; Henshall, S. M.; Tran, T.; Lin, J.; Quong, A.; Comstock, C. E S; Witkiewicz, A.; Musgrove, E. A.; Rui, H.; Lemarchand, L.; Setiawan, V. W.; Haiman, C. A.; Knudsen, K. E.; Sutherland, R. L.; Knudsen, E. S.

In: Oncogene, Vol. 28, No. 15, 16.04.2009, p. 1812-1820.

Research output: Contribution to journalArticle

Millar, EKA, Dean, JL, McNeil, CM, O'Toole, SA, Henshall, SM, Tran, T, Lin, J, Quong, A, Comstock, CES, Witkiewicz, A, Musgrove, EA, Rui, H, Lemarchand, L, Setiawan, VW, Haiman, CA, Knudsen, KE, Sutherland, RL & Knudsen, ES 2009, 'Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome', Oncogene, vol. 28, no. 15, pp. 1812-1820. https://doi.org/10.1038/onc.2009.13
Millar, E. K A ; Dean, J. L. ; McNeil, C. M. ; O'Toole, S. A. ; Henshall, S. M. ; Tran, T. ; Lin, J. ; Quong, A. ; Comstock, C. E S ; Witkiewicz, A. ; Musgrove, E. A. ; Rui, H. ; Lemarchand, L. ; Setiawan, V. W. ; Haiman, C. A. ; Knudsen, K. E. ; Sutherland, R. L. ; Knudsen, E. S. / Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. In: Oncogene. 2009 ; Vol. 28, No. 15. pp. 1812-1820.
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