Intrinsic apoptotic pathway activation increases response to anti-estrogens in luminal breast cancers.

Although the trend towards BIK upregulation in HCC1428-LTED cells over parental HCC1428 cells did not reach statistical significance, together these findings suggest that ERα+ breast cancer cells respond to sustained estrogen deprivation through BIK and Mcl-1 upregulation. 33 , 34 Mcl-1 upregulation upon sustained estrogen deprivation was confirmed by immunohistochemical staining in MCF7 xenografts grown in ovariectomized hosts (thus, estrogen deprived for 42 days), revealing increased Mcl-1 staining intensity, as compared to MCF7 xenografts grown in ovariectomized hosts supplemented with 42-day release estrogen pellets (Fig. 2b , and Supplemental Figure S3b ).

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