Identification of Novel Variants of the CB1 Cannabinoid Receptor in Cancer Cells

Abstract

Cannabinoid receptors (CBRs) are G‐protein coupled receptors (GPCRs) that are activated by the binding of cannabinoid ligands. It has recently been shown that CB1, found mostly in the brain, and CB2, found mostly in white blood cells and the spleen, have been found to be overexpressed in different cancer models. It has been found that besides the wild‐type CB1, different, shorter versions of the CB1 protein, called CB1 splice variants, are also found in the human brain. However, their function is unknown and requires further investigation. Currently, there is no information available on the expression of these CB1 variants in cancer. Preliminary results using semi‐quantitative reverse transcription polymerase chain reaction (RTPCR) utilizing primers corresponding to CB1 brain variants was used to demonstrate that in several cancer lines of brain, pancreatic, and breast tissue, there were CB1 transcripts of varying sizes were, in fact, being expressed. High, inter‐cancer variations were observed; some cancer lines did not possess any of the constructs while others expressed brain specific variants, and some lines even expressed other potential variants of differing lengths. Based upon our analysis of the results, we hypothesize that in these cancer cells, variants identical to those observed in the brain were being expressed, and that different, cancer‐specific CB1 variants were also being expressed. Currently, we are identifying numerous PCR products obtained by cloning and sequencing. Eventually, the isolated novel variant CBR1 genes will be overexpressed in mammalian cells, and functional analysis of each variant receptor conducted. If successful, the physiological significance of these splice variants and their use as potential novel targets for cannabinoid anti‐cancer drug developments will be determined.Support or Funding Information[DoD‐W81XWH1110795, UAMS TRI ABCRP to AR‐P, P20 RR‐16460 INBRE, NIH/NIDA DA039143 to ARP and PLP]