Notably, some carcinomas not only fail to become growth-inhibited upon treatment with RA, but instead respond to RA treatment with enhanced proliferation ( 16, 17). The data demonstrate the existence of a mechanism that underlies RA resistance in tumors, indicate that CRABP-II functions as a tumor suppressor, and suggest that the inhibition of FABP5 may comprise a therapeutic strategy for overcoming RA resistance in some tumors.

Decreasing this ratio in mammary tissue diverted RA from PPARβ/δ to RAR and suppressed tumor growth. This behavior was traced to an aberrantly high intratumor FABP5/CRABP-II ratio. Here, we show that, in the RA-resistant mouse model of breast cancer MMTV-neu, RA indeed activates the nonclassical RA receptor PPARβ/δ. The observations that partitioning of RA between its two receptors is regulated by two intracellular lipid-binding proteins-CRABP-II, which targets RA to RAR, and FABP5, which delivers it to PPARβ/δ-further suggest that RA resistance may stem from the deregulation of the binding proteins, resulting in activation of PPARβ/δ rather than RAR. A clue to this paradoxical behavior was recently suggested by the findings that RA also activates PPARβ/δ, a receptor involved in mitogenic and anti-apoptotic activities. Moreover, in some cancers, RA facilitates rather than inhibits growth. However, use of RA in oncology is limited by RA resistance acquired during carcinogenesis. Retinoic acid (RA) displays potent anticarcinogenic activities that are mediated by the nuclear retinoic acid receptors (RARs).

Oh no it red rat rar