Supplementary Table 6B from B-Raf Activation Cooperates with PTEN Loss to Drive c-Myc Expression in Advanced Prostate Cancer

Wang, Jingqiang; Kobayashi, Takashi; Floc'h, Nicolas; Kinkade, Carolyn Waugh; Aytes, Alvaro; Dankort, David; Lefebvre, Celine; Mitrofanova, Antonina; Cardiff, Robert D.; McMahon, Martin; Califano, Andrea; Shen, Michael M.; Abate-Shen, Cory

doi:10.1158/0008-5472.22394093.v1

00085472can120820-sup-t6b_31k.pdf (35.52 kB)

Supplementary Table 6B from B-Raf Activation Cooperates with PTEN Loss to Drive c-Myc Expression in Advanced Prostate Cancer

journal contribution

posted on 2023-03-30, 21:22 authored by Jingqiang Wang, Takashi Kobayashi, Nicolas Floc'h, Carolyn Waugh Kinkade, Alvaro Aytes, David Dankort, Celine Lefebvre, Antonina Mitrofanova, Robert D. Cardiff, Martin McMahon, Andrea Califano, Michael M. Shen, Cory Abate-Shen

PDF file - 31K, Myc pathway enrichment analysis for differentially expressed genes between RAP + PD treated and Vehicle treated Nkx3.1CE2/+; Ptenf/f; BrafCA/+ mouse prostate tumors

History

ARTICLE ABSTRACT

Both the PI3K → Akt → mTOR and mitogen-activated protein kinase (MAPK) signaling pathways are often deregulated in prostate tumors with poor prognosis. Here we describe a new genetically engineered mouse model of prostate cancer in which PI3K-Akt-mTOR signaling is activated by inducible disruption of PTEN, and extracellular signal-regulated kinase 1/2 (ERK1/2) MAPK signaling is activated by inducible expression of a BRAFV600E oncogene. These tissue-specific compound mutant mice develop lethal prostate tumors that are inherently resistant to castration. These tumors bypass cellular senescence and disseminate to lymph nodes, bone marrow, and lungs where they form overt metastases in approximately 30% of the cases. Activation of PI3K → Akt → mTOR and MAPK signaling pathways in these prostate tumors cooperate to upregulate c-Myc. Accordingly, therapeutic treatments with rapamycin and PD0325901 to target these pathways, respectively, attenuate c-Myc levels and reduce tumor and metastatic burden. Together, our findings suggest a generalized therapeutic approach to target c-Myc activation in prostate cancer by combinatorial targeting of the PI3K → Akt → mTOR and ERK1/2 MAPK signaling pathways. Cancer Res; 72(18); 4765–76. ©2012 AACR.