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

摘要

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.