Suppression of Her2/Neu mammary tumor development in mda-7/IL-24 transgenic mice

摘要: // You-Jun Li 1,* , Guodong Liu 2,* Lei Xia 4 Xiao Jeff C. 5 Mitchell E. Menezes 6 Swadesh K. Das Luni Emdad Devanand Sarkar Paul B. Fisher Michael Archer 2,3 Eldad Zacksenhaus 3,5 and Yaacov Ben-David 3,4 1 Department of Anatomy, Norman Bethune College Medicine, Jilin University, Changchun, Jilin, China 2 Nutritional Sciences, University Toronto, Ontario, Canada 3 Medical Biophysics, Division Biology, The Key Laboratory Chemistry for Natural Products Guizhou Province Chinese Academy Guiyang, Toronto General Research Institute - Health Network, Human Molecular Genetics, VCU Massey Cancer Center, Virginia Commonwealth School Richmond, Virginia, USA * These authors have contributed equally to this work Correspondence to: Ben-David, email: Zacksenhaus, Keywords : mda-7/IL-24, HER2, breast cancer, prevention, mouse model Received July 06, 2015 Accepted September 23, Published October 09, Abstract Melanoma differentiation associated gene-7/interleukin-24 ( mda-7/IL-24 ) encodes a tumor suppressor gene implicated in the growth various types including cancer. We previously demonstrated that recombinant adenovirus-mediated expression mammary glands carcinogen-treated (methylnitrosourea, MNU) rats suppressed development. Since most MNU-induced tumors contain activating mutations Ha-ras, which arenot frequently detected humans, we presently examined effect MDA-7/IL-24 on Her2/Neu induced tumors, RAS pathway is induced. generated tet-inducible transgenic mice crossed them with mice. Triple compound treated doxycycline exhibited strong inhibition development, demonstrating activity by immune-competent induction also inhibited following injection cells isolated from triple had not been doxycycline, into fat pads isogenic FVB Despite initial suppression, lost grew, albeit after longer latency, indicating continuous presence cytokine within microenvironment crucial sustain inhibitory activity. Mechanistically, exerted its suppression HER2 + cancer cells, at least part, through PERP, member PMP-22 family arrest apoptosis-inducing capacity. Overall, our results establish as development provide rationale using prevention/treatment human