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PMID: 19383354 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer.

Molecular oncology ·Vol. 2 ·No. 4 ·2008-12-00 ·Pages 327-39

Bergamaschi A, Kim YH, Kwei KA, La Choi Y, Bocanegra M, Langerød A, Han W, Noh DY, Huntsman DG, Jeffrey SS, Børresen-Dale AL, Pollack JR

Abstract

Breast cancer exhibits clinical and molecular heterogeneity, where expression profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new opportunities for therapy. To identify the driver oncogene on 10p associated with basal-like tumors, we analyzed genomic profiles of 172 breast carcinomas. The smallest shared region of gain spanned just seven genes at 10p13, including calcium/calmodulin-dependent protein kinase ID (CAMK1D), functioning in intracellular signaling but not previously linked to cancer. By microarray, CAMK1D was overexpressed when amplified, and by immunohistochemistry exhibited elevated expression in invasive carcinomas compared to carcinoma in situ. Engineered overexpression of CAMK1D in non-tumorigenic breast epithelial cells led to increased cell proliferation, and molecular and phenotypic alterations indicative of epithelial-mesenchymal transition (EMT), including loss of cell-cell adhesions and increased cell migration and invasion. Our findings identify CAMK1D as a novel amplified oncogene linked to EMT in breast cancer, and as a potential therapeutic target with particular relevance to clinically unfavorable basal-like tumors.

MeSH Terms
Breast Neoplasms/pathology Calcium-Calmodulin-Dependent Protein Kinase Type 1/analysis,genetics Cell Adhesion/genetics Cell Proliferation Chromosomes, Human, Pair 10/genetics Epithelial Cells/pathology Female Gene Amplification Humans Immunohistochemistry Mesenchymal Stem Cells/classification,pathology Neoplasm Invasiveness/genetics Oligonucleotide Array Sequence Analysis
Chemicals
CAMK1D protein, human Calcium-Calmodulin-Dependent Protein Kinase Type 1
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Bergamaschi Anna
Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Kim Young H
Kwei Kevin A
La Choi Yoon
Bocanegra Melanie
Langerød Anita
Han Wonshik
Noh Dong-Young
Huntsman David G
Jeffrey Stefanie S
Børresen-Dale Anne-Lise
Pollack Jonathan R
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Article Info
Journal
Molecular oncology
Abbr.
Mol Oncol
ISSN
1878-0261
DOI
10.1016/j.molonc.2008.09.004
Published
2008-12-00
Epub
2008-00-02
Pages
327-39
Language
English
Region
United States
NLM ID
101308230
PMCID
PMC2653212
Subset
IM
Grants
NCI NIH HHS · R01 CA112016 · United States
NCI NIH HHS · T32 CA009302 · United States
NCI NIH HHS · R01 CA097139-05 · United States
NCI NIH HHS · R01 CA097139 · United States
NCI NIH HHS · CA112016 · United States
External Links
PubMed source DOI: 10.1016/j.molonc.2008.09.004 PMC Full Text View journal details
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