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. 2020 Aug 14;12(8):2275. doi: 10.3390/cancers12082275

Figure 3.

Figure 3

The RA-RARA-ANXA8 mechanism in normal and aberrant mammary morphogenesis. (A) Confocal microscopy images (scale bar: 10 µm) showing that normal human mammary epithelial (HME1) cells with normal RARA functions develop 3D acinar structures with a lumen lined by ANXA8-positive cells (left column). HME1 cells with RARA403 or PI3KCAH1047R mutations develop ANXA8-positive, morphologically aberrant 3D acinar structures (middle and right columns) [110]. (B) Microscopy images of the fourth mammary gland section of a 12-week-old FVB female mouse with wild type RARA and wild type PI3KCA showing a duct lined by ANXA8-positive cells (left column). In contrast, the fourth mammary gland of 12-week-old FVB female mice expressing either MMTV-RARA403 or MMTV-PI3KCAH1047R mutations showed ductal hyperplasia (DH) with ANXA8-positive cells in the luminal space (middle and right columns) (scale bar: 30 µm) (our unpublished images). (C) The interdependence of a functional RA-RARA mechanism and baseline ANXA8 expression generates normal morphogenesis (left scheme). In contrast, a defective RA-RARA mechanism upregulating endogenous ANXA8 generates aberrant morphogenesis (right scheme).