Ductal carcinoma in situ (
DCIS) is a nonmalignant lesion of the breast with the potential to progress to invasive
ductal carcinoma (IDC). The disappearance and breakdown of the myoepithelial cell layer and basement membrane in
DCIS have been identified as major events in the development of
breast cancer. The MCF10DCIS.com cell line is a well-established model, which recapitulates the progression of
breast cancer from
DCIS to IDC. We have previously reported that a novel Gemini
vitamin D analog, 1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (
BXL0124) is a potent inhibitor of the growth of MCF10DCIS.com xenografted
tumors without hypercalcemic toxicity. In this study, we utilized the MCF10DCIS.com in vivo model to assess the effects of
BXL0124 on
breast cancer progression from weeks 1 to 4. Upon
DCIS progression to IDC from weeks 3 to 4,
tumors lost the myoepithelial cell layer and basement membrane as shown by immunofluorescence staining with smooth muscle actin and
laminin 5, respectively. Administration of
BXL0124 maintained the critical myoepithelial cell layer as well as basement membrane, and animals treated with
BXL0124 showed a 43% reduction in
tumor volume by week 4.
BXL0124 treatment decreased cell proliferation and maintained
vitamin D receptor levels in
tumors. In addition, the
BXL0124 treatment reduced the
mRNA levels of
matrix metalloproteinases starting at week 3, contributing to the inhibition of invasive transition. Our results suggest that the maintenance of
DCIS plays a significant role in the
cancer preventive action of the Gemini
vitamin D BXL0124 during the progression of breast lesions.