1: Br J Cancer. 2005 Aug 8;93(3):310-8. 

The retinoid anticancer signal: mechanisms of target gene regulation.

Liu T, Bohlken A, Kuljaca S, Lee M, Nguyen T, Smith S, Cheung B, Norris MD,
Haber M, Holloway AJ, Bowtell DD, Marshall GM.

Children's Cancer Institute Australia for Medical Research, Randwick NSW 2031,
Australia.

Retinoids induce growth arrest, differentiation, and cell death in many cancer
cell types. One factor determining the sensitivity or resistance to the retinoid
anticancer signal is the transcriptional response of retinoid-regulated target
genes in cancer cells. We used cDNA microarray to identify 31 retinoid-regulated
target genes shared by two retinoid-sensitive neuroblastoma cell lines, and then
sought to determine the relevance of the target gene responses to the retinoid
anticancer signal. The pattern of retinoid responsiveness for six of 13 target
genes (RARbeta2, CYP26A1, CRBP1, RGS16, DUSP6, EGR1) correlated with phenotypic
retinoid sensitivity, across a panel of retinoid-sensitive or -resistant lung
and breast cancer cell lines. Retinoid treatment of MYCN transgenic mice bearing
neuroblastoma altered the expression of five of nine target genes examined
(RARbeta2, CYP26A1, CRBP1, DUSP6, PLAT) in neuroblastoma tumour tissue in vivo.
In retinoid-sensitive neuroblastoma, lung and breast cancer cell lines, direct
inhibition of retinoid-induced RARbeta2 expression blocked induction of only one
of eight retinoid target genes (CYP26A1). DNA demethylation, histone
acetylation, and exogenous overexpression of RARbeta2 partially restored
retinoid-responsive CYP26A1 expression in RA-resistant MDA-MB-231 breast, but
not SK-MES-1 lung, cancer cells. Combined, rather than individual, inhibition of
DUSP6 and RGS16 was required to block retinoid-induced growth inhibition in
neuroblastoma cells, through phosphorylation of extracellular-signal-regulated
kinase. In conclusion, sensitivity to the retinoid anticancer signal is
determined in part by the transcriptional response of key retinoid-regulated
target genes, such as RARbeta2, DUSP6, and RGS16.

PMID: 16012519 [PubMed - indexed for MEDLINE]


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2: Clin Cancer Res. 2004 Oct 15;10(20):6789-95. 

Molecular profiling of inflammatory breast cancer: identification of a
poor-prognosis gene expression signature.

Bieche I, Lerebours F, Tozlu S, Espie M, Marty M, Lidereau R.

Laboratoire d'Oncogenetique - INSERM E0017, Centre Rene Huguenin, St-Cloud,
France. i.bieche@stcloud-huguenin.org

PURPOSE: Inflammatory breast cancer (IBC) is a rare but particularly aggressive
form of primary breast cancer. The molecular mechanisms responsible for IBC are
largely unknown. EXPERIMENTAL DESIGN: To obtain further insight into the
molecular pathogenesis of IBC, we used real-time quantitative reverse
transcription (RT)-PCR to quantify the mRNA expression of 538 selected genes in
IBC relative to non-IBC. RESULTS: Twenty-seven (5.0%) of the 538 genes were
significantly up-regulated in IBC compared with non-IBC. None were
down-regulated. The 27 up-regulated genes mainly encoded transcription factors
(JUN, EGR1, JUNB, FOS, FOSB, MYCN, and SNAIL1), growth factors (VEGF,
DTR/HB-EGF, IGFBP7, IL6, ANGPT2, EREG, CCL3/MIP1A, and CCL5/RANTES) and growth
factor receptors (TBXA2R, TNFRSF10A/TRAILR1, and ROBO2). We also identified a
gene expression profile, based on MYCN, EREG, and SHH, which discriminated
subgroups of IBC patients with good, intermediate, and poor outcome. CONCLUSION:
Our study has identified a limited number of signaling pathways that require
inappropriate activation for IBC development. Some of the up-regulated genes
identified here could offer useful diagnostic or prognostic markers and could
form the basis of novel therapeutic strategies.

PMID: 15501955 [PubMed - indexed for MEDLINE]


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