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Series GSE9867

Query DataSets for GSE9867

Status

Public on Jun 01, 2008

Title

Understanding Vitamin D resistance using expression microarrays

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Vitamin D is the strongest known natural anti-proliferative. A large number of studies in a wide spectrum of cancers, including epidemiological, in vitro and animal models, demonstrate that the active form of Vitamin D has anti-cancer benefits, affecting both progression and metastasis. Alike the role in calcium Vitamin D regulation, its anti-proliferative effect is thought to function through the Vitamin D receptor (VDR), although convincing evidence is lacking. Notwithstanding, separation of the calcemic and the anti-proliferative activity of Vitamin D analogues has been a major obstacle in developing new drugs for the treatment of cancer.
The work presented attempts to unveil the molecular mechanism behind the anti-proliferative action of Vitamin D using genomic tools. For that purpose four independently developed Vitamin D sensitive/resistant MCF7 cell line pairs were collected. These unique biological replicates enabled us, both to increase the power of our study and to omit the use of Vitamin D. We deem this omission crucial since in the presence of Vitamin D only downstream genes involved in proliferation and cell cycle would be identified rather than causal resistance genes. The use of a variety of genomic techniques including expression, NMD and oligo CGH arrays reveal in the resistant cell lines the 11q13-14 as a region of DNA copy number loss and an altered expression of EGFR signaling pathway genes. Surprisingly, no genes known from calcium Vitamin D regulation were identified, nor did the VDR silencing by RNAi induce resistance to the sensitive cell lines.
Keywords: Expression microarray, cell type comparision

Overall design

Several MCF7 breast tumor cell lines independently derived from the human breast cancer cell line, both resistant and sensitive to Vitamin D, were used. The pairs of cell lines (parental-resistant) were developed in different laboratories and using different methodologies; while some cell lines acquired resistance by long exposure to the physiological concentration of Vitamin D (100nM), others were induced to resistant by being exposed to increasing amounts of Vitamin D. A total of 14 microarray expression experiments were carried out, including four biological replicates and 10 technical replicates including dye swaps. In all microarray experiments RNA from the Vitamin D resistant cell line was hybrizided agains RNA from the respsective sensitive/parental cell line.

Contributor(s)

Costa JL, Eijk P, van de Wiel M, ten Berge D, Schmitt F, Narvaez CJ, Welsh J, Ylstra B

Citation(s)

19863778

Submission date

Dec 13, 2007

Last update date

Mar 17, 2012

Contact name

Daoud Sie

E-mail(s)

d.sie@vumc.nl