Research Paper Volume 12, Issue 24 pp 24671—24692
Progesterone receptor isoform-dependent cross-talk between prolactin and fatty acid synthase in breast cancer
- 1 Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain
- 2 Girona Biomedical Research Institute (IDIBGI), Girona, Spain
- 3 Peirce Medical Communications, Clemson, SC 29634, USA
- 4 Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
- 5 Mayo Clinic, Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Rochester, MN 55905, USA
- 6 Stem Cells Laboratory, Institute of Biology and Experimental Medicine (IBYME-CONICET), Buenos Aires, Argentina
- 7 Department of Biological Sciences, Clemson University, Greenville, SC 29634, USA
- 8 Mayo Clinic Minnesota, Department of Biochemistry and Molecular Biology Laboratory, Rochester, MN 55905, USA
- 9 Mayo Clinic Cancer Center, Rochester, MN 55905, USA
Received: September 23, 2020 Accepted: October 27, 2020 Published: December 10, 2020https://doi.org/10.18632/aging.202289
How to Cite
Copyright: © 2020 Menendez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Progesterone receptor (PR) isoforms can drive unique phenotypes in luminal breast cancer (BC). Here, we hypothesized that PR-B and PR-A isoforms differentially modify the cross-talk between prolactin and fatty acid synthase (FASN) in BC. We profiled the responsiveness of the FASN gene promoter to prolactin in T47Dco BC cells constitutively expressing PR-A and PR-B, in the PR-null variant T47D-Y cell line, and in PR-null T47D-Y cells engineered to stably re-express PR-A (T47D-YA) or PR-B (T47D-YB). The capacity of prolactin to up-regulate FASN gene promoter activity in T47Dco cells was lost in T47D-Y and TD47-YA cells. Constitutively up-regulated FASN gene expression in T47-YB cells and its further stimulation by prolactin were both suppressed by the prolactin receptor antagonist hPRL-G129R. The ability of the FASN inhibitor C75 to decrease prolactin secretion was more conspicuous in T47-YB cells. In T47D-Y cells, which secreted notably less prolactin and downregulated prolactin receptor expression relative to T47Dco cells, FASN blockade resulted in an augmented secretion of prolactin and up-regulation of prolactin receptor expression. Our data reveal unforeseen PR-B isoform-specific regulatory actions in the cross-talk between prolactin and FASN signaling in BC. These findings might provide new PR-B/FASN-centered predictive and therapeutic modalities in luminal intrinsic BC subtypes.