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JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells.
Oncogene. 2008 Aug 28; 27(37):5033-44.O

Abstract

It has been recently shown that cannabinoids, the active components of marijuana and their derivatives, inhibit cell cycle progression of human breast cancer cells. Here we studied the mechanism of Delta(9)-tetrahydrocannabinol (THC) antiproliferative action in these cells, and show that it involves the modulation of JunD, a member of the AP-1 transcription factor family. THC activates JunD both by upregulating gene expression and by translocating the protein to the nuclear compartment, and these events are accompanied by a decrease in cell proliferation. Of interest, neither JunD activation nor proliferation inhibition was observed in human non-tumour mammary epithelial cells exposed to THC. We confirmed the importance of JunD in THC action by RNA interference and genetic ablation. Thus, in both JunD-silenced human breast cancer cells and JunD knockout mice-derived immortalized fibroblasts, the antiproliferative effect exerted by THC was significantly diminished. Gene array and siRNA experiments support that the cyclin-dependent kinase inhibitor p27 and the tumour suppressor gene testin are candidate JunD targets in cannabinoid action. In addition, our data suggest that the stress-regulated protein p8 participates in THC antiproliferative action in a JunD-independent manner. In summary, this is the first report showing not only that cannabinoids regulate JunD but, more generally, that JunD activation reduces the proliferation of cancer cells, which points to a new target to inhibit breast cancer progression.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18454173

Citation

Caffarel, M M., et al. "JunD Is Involved in the Antiproliferative Effect of Delta9-tetrahydrocannabinol On Human Breast Cancer Cells." Oncogene, vol. 27, no. 37, 2008, pp. 5033-44.
Caffarel MM, Moreno-Bueno G, Cerutti C, et al. JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008;27(37):5033-44.
Caffarel, M. M., Moreno-Bueno, G., Cerutti, C., Palacios, J., Guzman, M., Mechta-Grigoriou, F., & Sanchez, C. (2008). JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene, 27(37), 5033-44. https://doi.org/10.1038/onc.2008.145
Caffarel MM, et al. JunD Is Involved in the Antiproliferative Effect of Delta9-tetrahydrocannabinol On Human Breast Cancer Cells. Oncogene. 2008 Aug 28;27(37):5033-44. PubMed PMID: 18454173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. AU - Caffarel,M M, AU - Moreno-Bueno,G, AU - Cerutti,C, AU - Palacios,J, AU - Guzman,M, AU - Mechta-Grigoriou,F, AU - Sanchez,C, Y1 - 2008/05/05/ PY - 2008/5/6/pubmed PY - 2008/9/25/medline PY - 2008/5/6/entrez SP - 5033 EP - 44 JF - Oncogene JO - Oncogene VL - 27 IS - 37 N2 - It has been recently shown that cannabinoids, the active components of marijuana and their derivatives, inhibit cell cycle progression of human breast cancer cells. Here we studied the mechanism of Delta(9)-tetrahydrocannabinol (THC) antiproliferative action in these cells, and show that it involves the modulation of JunD, a member of the AP-1 transcription factor family. THC activates JunD both by upregulating gene expression and by translocating the protein to the nuclear compartment, and these events are accompanied by a decrease in cell proliferation. Of interest, neither JunD activation nor proliferation inhibition was observed in human non-tumour mammary epithelial cells exposed to THC. We confirmed the importance of JunD in THC action by RNA interference and genetic ablation. Thus, in both JunD-silenced human breast cancer cells and JunD knockout mice-derived immortalized fibroblasts, the antiproliferative effect exerted by THC was significantly diminished. Gene array and siRNA experiments support that the cyclin-dependent kinase inhibitor p27 and the tumour suppressor gene testin are candidate JunD targets in cannabinoid action. In addition, our data suggest that the stress-regulated protein p8 participates in THC antiproliferative action in a JunD-independent manner. In summary, this is the first report showing not only that cannabinoids regulate JunD but, more generally, that JunD activation reduces the proliferation of cancer cells, which points to a new target to inhibit breast cancer progression. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/18454173/JunD_is_involved_in_the_antiproliferative_effect_of_Delta9_tetrahydrocannabinol_on_human_breast_cancer_cells_ L2 - https://doi.org/10.1038/onc.2008.145 DB - PRIME DP - Unbound Medicine ER -