Antimetastatic gene expression profiles mediated by retinoic acid receptor beta 2 in MDA-MB-435 breast cancer cells

Abstract

BackgroundThe retinoic acid receptor beta 2 (RARβ2) gene modulates proliferation and survival of cultured human breast cancer cells. Previously we showed that ectopic expression of RARβ2 in a mouse xenograft model prevented metastasis, even in the absence of the ligand, all-trans retinoic acid. We investigated both cultured cells and xenograft tumors in order to delineate the gene expression profiles responsible for an antimetastatic phenotype.MethodsRNA from MDA-MB-435 human breast cancer cells transduced with RARβ2 or empty retroviral vector (LXSN) was analyzed using Agilent Human 1A Oligo microarrays. The one hundred probes with the greatest differential intensity (p < 0.004, jointly) were determined by selecting the top median log ratios from eight-paired microarrays. Validation of differences in expression was done using Northern blot analysis and quantitative RT-PCR (qRT-PCR). We determined expression of selected genes in xenograft tumors.ResultsRARβ2 cells exhibit gene profiles with overrepresentation of genes from Xq28 (p = 2 × 10-8), a cytogenetic region that contains a large portion of the cancer/testis antigen gene family. Other functions or factors impacted by the presence of exogenous RARβ2 include mediators of the immune response and transcriptional regulatory mechanisms. Thirteen of fifteen (87%) of the genes evaluated in xenograft tumors were consistent with differences we found in the cell cultures (p = 0.007).ConclusionAntimetastatic RARβ2 signalling, direct or indirect, results in an elevation of expression for genes such as tumor-cell antigens (CTAG1 and CTAG2), those involved in innate immune response (e.g., RIG-I/DDX58), and tumor suppressor functions (e.g., TYRP1). Genes whose expression is diminished by RARβ2 signalling include cell adhesion functions (e.g, CD164) nutritional or metabolic processes (e.g., FABP6), and the transcription factor, JUN.

Retinoic acid inducible gene-I, more than a virus sensor

“…Furthermore, RIG-I mediates the IFN-γ stimulation of ISG15 and CXCL11 in these cells, suggesting that RIG-I is involved in the immuno-modulatory function (Cui et al, 2004;Yuzawa et al, 2008). A micro-array screen of MDA-MB-435 human breast cancer cells showed that RIG-I is up-regulated in retinoic acid receptor β2 (RARβ2) transfected cells, indicating a possible role of RIG-I in antimetastasis (Wallden et al, 2005). Viral infection can lead to carcinogenesis.…”

Tumor-suppressive activity of retinoic acid receptor-β in cancer

“…Again, induction of RAR-β 2 expression suppressed the potential for metastasis of breast cancer cells. Another cDNA microarray study showed that RAR-β 2 induced the expression of tumor-cell antigens (CTAG1 and CTAG2), the innate immune response (e.g., RIG-I/DDX58), and a tumor suppressor gene (TYRP1) but reduced the expression of several genes involved in cell adhesion (LSAMP, PCDH11Y, and CD64), nutrient availability (FABP6, SLC38A2, PCSK4, SRPB1), and transcription/AP-1 activity (HOXB7 and JUN) [20].…”

“…Thus, the use of retinoids as chemopreventive agents in human cancers has gone from a zenith in the 1990s to something of a nadir nowadays. Current research efforts focus mainly on the molecular mechanisms underlying the actions of retinoids [16][17][18][19][20][21] and on use of retinoid X receptorselective or retinoid receptor-independent retinoids in the prevention of human cancers [22][23][24][25].…”

Dietary Small Molecules and Large-Scale Gene Expression Studies: An Experimental Approach for Understanding their Beneficial Effects on the Development of Malignant and Non-Malignant Proliferative Diseases

“…S100A4 serves as a molecular marker for development of tumours and the metastatic potential of tumours [90]; S100A2 is also expressed in different tumour cell types [91] TFF3 Trefoil factor-3: Function gene analysis by the interference RNA method demonstrated that knockdown of the expression resulted in an inhibition of the spheroid formation of tumour cells [92] IFI27 Interferon -inducible protein 27: An increased expression has been observed in different tumour cells [93] metabolomics are able to generate overwhelming datasets that cannot be analysed independently. Therefore, there is an emerging need for bioinformatics to interpret the obtained datasets in the field of nutritional science.…”