RARβ IN CANCER CELLS

Retinoic acid treatment of cancer cells:

• reduced DNA synthesis
• reduced cell proliferation
• morphological changes

In some cancer cell types, these changes do not occur, making the cell types retinoic acid resistant.

Many RA resistant cancer cells have reduced or no mRNA (or protein) levels of RARβ, and RARβ cannot be induced through RA treatment. This has been shown in cancer cells from breast, head and neck, lung, oral tissues, uterus and ovaries, and also in cancer samples from oesophagus, prostate, breast and lung.

How is the amount of RARβ reduced ?

• Chromosomal deletions or translocations of the RARβ gene have not been found that can explain the reduced RARβ expression.
• However, hypermethylation of the RARβ gene has been shown to possibly reduce expression of the gene.
• In addition, the demethylating agent 5-aza-2'-deoxycytidine can restore normal retinoic acid induceable RARβ expression.