Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

Abstract

We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2. The altered transcripts identified by microarray analysis were involved in cell-cell or cell-matrix interaction, Rho signaling, calcium homeostasis and copper-binding/sensitive activities. A set of nine genes that included GPCR11, cadherin 11, annexin A1, vimentin, lactate dehydrogenase B (upregulated in MDA-MB-231) and GREB1, S100A8, amyloid b precursor protein, claudin 3 and cadherin 1 (downregulated in MDA-MB-231) were sufficient to distinguish MDA-MB-231 from MCF7 cells. The downregulation of a set of transcripts for proteins involved in cell-cell interaction indicated these transcripts as potential markers for invasiveness that can be detected by methylation-specific PCR. The proteomic profiles indicated altered abundance of fewer proteins as compared to transcript profiles. Antisense knockdown of selected transcripts led to inhibition of cell proliferation that was accompanied by altered proteomic profiles. The proteomic profiles of antisense transfectants suggest the involvement of peptidyl-prolyl isomerase, Raf kinase inhibitor and 80 kDa protein kinase C substrate in mediating the inhibition of cell proliferation.

Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation

“…Reduced expression of claudin 7 was associated with invasion and metastasis of esophageal cancers (54). Claudin 3 was recently shown to be down-regulated in invasive, compared with noninvasive, breast cancer cells (55). Interestingly, claudin 6 expression, which we found to be highly up-regulated in the presence of wild-type BRCA1, was preferentially expressed in mammary epithelial cells from Copenhagen rats, which are resistant to mammary cancer, versus more susceptible Buffalo rats (56).…”

miR‐515‐5p controls cancer cell migration throughMARK4 regulation

“…As MCF7 cells are known to display poor motility, we did not analyse the effect of either miR‐515‐5p or MARK4 silencing on MCF7 cell migration 17. Hence, we limited our primary analysis to MDA‐MB‐231, A549 and H1299 cell lines.…”

Transcription factor Runx2 is a regulator of epithelial–mesenchymal transition and invasion in thyroid carcinomas

“…20 Runx2 expression is higher in prostate cancer and invasive breast cancer compared with corresponding non-neoplastic or non-invasive lesions. [23][24][25] Enhanced Runx2 expression in prostate cancer is associated with disease progression including higher Gleason scores. 8 In breast cancers with a high labeling index of Runx2, the clinical outcome of the breast cancer was worse; Runx2 is used as an independent prognostic factor in these patients.…”