Molecular characterization of breast cell lines: a tool for breast cancer studies

Background

Breast cancer is a complex, heterogeneous disease at the molecular level. Recent advances proposed a new molecular taxonomy of breast cancer that defines molecular subtypes such as luminal or basal-like cancers. Hopefully this may modify breast cancer management. A great part of our knowledge on breast carcinomas is based on studies of breast cancer cell lines (BCC). Although many data are available on BCC lines, less is actually known on their molecular characterization. We have determined the molecular subtype of 31 BCC using DNA microarrays and confirmed their phenotype by immunohistochemistry (IHC) on 'cell microarrays' (CMA).

Methods

DNA array results were obtained on an Affymetrix station. CMA was constructed in a paraffin block from an agarose core of cell line pellets. Proteins studied in IHC were: estrogen and progesterone receptors, transcription factors GATA 3 and GATA 4, tyrosine kinase receptors (EGFR, ERBB2, MET), sialomucin MUC1, luminal cyto-keratins CK8/18 and CK19, basal cytokeratins CK5/6 and CK14, CALLA receptor (CD10), caveolae receptors CAV1 and CAV2, mesenchymal vimentin and alpha smooth actin.

Results

Hierarchical clustering sharply discriminated two groups of BCC. To determine whether a BCC was of 'luminal' or 'basal-like' subtype, hierarchical clustering was done with the subset of genes selected by Sørlie and colleagues to discriminate molecular subtypes of tumors: eight BCC were luminal-like, 12 were basal-like, and 11 were not clearly affected to one subtype. Supervised analysis selected the most discriminant genes between basal and luminal subtypes, and corresponding antibodies were tested on CMA when available. The immunohistochemical profile was in accordance with the transcriptional profile.

Conclusion

According to the molecular classification of breast tumors, we have determined two different subtypes of cell lines, luminal and basal-like, and isolated a subset of genes that discriminates both subtypes. The DNA array data were confirmed at the protein level. This characterization of breast cell lines provides a powerful tool to study specifically each molecular subtype of breast cancers. The master genes isolated from each group may be new targets for breast cancer management.