Retinoic Acid Prevents Precancerous Breast Cells from Progressing to Full-Blown Cancer

The model system consisted of four distinct cell lines which demonstrated a progressive neoplastic transformation: MCF-10F, normal stage; trMCF, transformed MCF-10F; bsMCF, invasive stage; and caMCF, tumorigenic stage. In three-dimensional cultures, MCF-10F cells formed tubules resembling the structures in the normal mammary gland. After treatment with estradiol, these cells formed tubules and spherical masses which were indicative of transformation.

In the current study the investigators evaluated the effect of all trans-retinoic acid (ATRA) at different stages of neoplastic transformation. Retinoids have been used as potential chemotherapeutic or chemopreventive agents because of their differentiative, antiproliferative, proapoptotic, and antioxidant properties.

Cells that only formed spherical masses in collagen were isolated (trMCF clone 11) and treated with ATRA. After treatment with a concentration of one micromolar ATRA, the trMCF clone 11 cells showed tubules in collagen. Gene expression studies showed that 207 genes upregulated in transformed trMCF clone 11 cells were downregulated after one micromolar ATRA treatment to levels comparable to those found in the normal breast epithelial cells MCF-10F. Furthermore, 236 genes that were downregulated in trMCF clone 11 were upregulated after one micromolar ATRA treatment to similar levels shown in normal epithelial cells. These 443 genes defined a signature of the ATRA reprogramming effect.

Results published in the March 21, 2014, edition of the International Journal of Oncology showed that one micromolar ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process and antagonistically regulate breast cancer associated genes. On the other hand, the invasive and tumorigenic cells did not show any changes in morphology after ATRA treatment.

“It looks like retinoic acid exerts effects on cancer cells in part via the modulation of the epigenome,” said senior author Dr. Sandra V. Fernandez, assistant research professor of medical oncology at Thomas Jefferson University. “We were able to see this effect of retinoic acid because we were looking at four distinct stages of breast cancer. It will be interesting to see if these results can be applied to patients.”

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