IPH-926 lobular breast cancer cells are triple-negative but their microarray profile uncovers a luminal subtype

Human primary breast cancers and breast cancer cell lines are classified by microarray-defined molecular subtypes, which reflect differentiation characteristics. Estrogen receptor (ER) expression is indicative of the luminal molecular subtype. We have previously established IPH-926, the first well-characterized cell line from infiltrating lobular breast cancer. IPH-926 displays an ER/PR/ErbB2 triple-negative immunophenotype, which is due to a loss of ER expression in its in vivo clonal ancestry. Loss of ER might indicate a fundamental change of cellular differentiation and it is unclear whether a luminal subtype is preserved beyond ER conversion. Using Affymetrix microarray analysis, seven different classifier gene lists (PAM305, DISC256, TN1288, PAM50, UNC1300, LAB704, INT500) and a background population of 50 common mammary carcinoma cell lines, we have now determined the molecular subtype of IPH-926. Strikingly, the IPH-926 expression profile is highly consistent with a luminal subtype. It is nearest to luminal/ER-positive breast cancer cell lines and far apart from basal breast cancer cell lines. Quantitative real-time RT-PCR confirmed enhanced expression of luminal marker genes (AGR2, CLU, CA12, EMP2, CLDN3) and low or absent expression of basal marker genes (KRT5, CD44, CAV1, VIM). Moreover, IPH-926 lacked androgen receptor (AR) expression, a transcription factor previously associated with luminal-like gene expression in a subset of triple-negative or molecular apocrine breast cancers. In conclusion, IPH-926 is triple-negative but belongs to the luminal subtype. Luminal differentiation characteristics can be preserved beyond ER conversion and might not require a compensatory expression of AR.