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Br J Cancer. 2014 Jul 15;111(2):326-38. doi: 10.1038/bjc.2014.297. Epub 2014 Jun 5.

Nuclear CSPP1 expression defined subtypes of basal-like breast cancer.

Author information

1
Department of Radiation Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway.
2
1] Departments of Genetics, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway [2] Department of Pathology, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway [3] K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, N-0310 Oslo, Norway.
3
Center for Cancer Systems Biology, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
1] Department of Pathology, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway [2] Institute for Medical Informatics, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway.
5
1] Departments of Genetics, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals - Norwegian Radium Hospital, N-0310 Oslo, Norway [2] K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, N-0310 Oslo, Norway.
6
1] Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, UK [2] Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [3] Cambridge Breast Unit, Addenbrooke's Hospital and Cambridge National Institute for Health Research Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.

Abstract

BACKGROUND:

The multi-exon CSPP1 gene, encoding for centrosome and microtubule-associated proteins involved in ciliogenesis and cell division, is a candidate oncogene in luminal breast cancer but expression of CSPP1 proteins remained unexplored.

METHODS:

CSPP1 gene and protein expression was examined in normal mammary tissue, human breast cancer cell lines, and primary breast cancer biopsies from two patient cohorts. Cell type and epitope-dependent subcellular-specific CSPP1 staining pattern in normal mammary gland epithelium and cancer biopsies were correlated to molecular and clinical parameters.

RESULTS:

A novel, nuclear localised CSPP1 isoform was exclusively detected in luminal epithelial cells, whereas cytoplasmic CSPP-L was generally expressed in normal mammary epithelium. Luminal cell-related nuclear CSPP1 expression was preserved in type-matched cell lines and carcinomas, and correlated to gene copy number and mRNA expression. In contrast, basal-like carcinomas displayed generally lower CSPP1 mRNA expression. Yet, a subgroup of basal-like breast carcinomas depicted nuclear CSPP1 expression, displayed luminal traits, and differed from nuclear CSPP1 devoid counterparts in expression of eight genes. Eight-gene signature defined groups of basal-like tumours from an independent cohort showed significant differences in survival.

CONCLUSIONS:

Differential expression of a nuclear CSPP1 isoform identified biologically and clinically distinct subgroups of basal-like breast carcinoma.

PMID:
24901235
PMCID:
PMC4102947
DOI:
10.1038/bjc.2014.297
[Indexed for MEDLINE]
Free PMC Article

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