Trastuzumab resistant cells maintain HER signaling. Lapatinib and combination resistant cells express up-regulated ER activity. (A) qRT-PCR expression levels of ER and PR mRNA in UACC-812 and BT474 parental and distinct resistant clones. Data were normalized to parental cells. (B) UACC-812 and BT474 parental cells were treated with trastuzumab (10 μg/ml), lapatinib (1 μM), or trastuzumab plus lapatinib for five hours and harvested. Whole-cell extracts of these treatment groups and resistant derivatives were analyzed by Western blot with the indicated antibodies.