@article{7ae2160ae940465c8fb3f0f705833390,
title = "Progesterone receptor isoform-dependent cross-talk between prolactin and fatty acid synthase in breast cancer",
abstract = "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",
keywords = "G129R, endocrine therapy, luminal breast cancer, prolactin receptor, prolactin receptor",
author = "Menendez, {Javier A.} and Peirce, {Susan K.} and Adriana Papadimitropoulou and Elisabet Cuy{\`a}s and Steen, {Travis Vander} and Sara Verdura and Luciano Vellon and Chen, {Wen Y.} and Ruth Lupu",
note = "Funding Information: This work was supported by the National Institute of Health/National Cancer Institute Grant R01 CA116623 (Ruth Lupu) and by the Department of Defense (DOD)-Breakthrough 3 Grants BC151072 and BC151072P1 (Ruth Lupu). Work in the Menendez laboratory is supported by the Spanish Ministry of Science and Innovation (Grants SAF2016-80639-P and PID2019-10455GB-I00, Plan Nacional de l+D+I, founded by the European Regional Development Fund, Spain) and by an unrestricted research grant from the Fundaci{\'o} Oncolliga Girona (Lliga catalana d{\textquoteright}ajuda al malalt de c{\`a}ncer, Girona). Funding Information: This work was supported by the National Institute of Health/National Cancer Institute Grant R01 CA116623 (Ruth Lupu) and by the Department of Defense (DOD)-Breakthrough 3 Grants BC151072 and BC151072P1 (Ruth Lupu). Work in the Menendez laboratory is supported by the Spanish Ministry of Science and Innovation (Grants SAF2016-80639-P and PID2019-10455GB-I00, Plan Nacional de l+D+I, founded by the European Regional Development Fund, Spain) and by an unrestricted research grant from the Fundaci? Oncolliga Girona (Lliga catalana d?ajuda al malalt de c?ncer, Girona). Publisher Copyright: {\textcopyright} 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.",
year = "2020",
month = dec,
day = "31",
doi = "10.18632/aging.202289",
language = "English (US)",
volume = "12",
pages = "24671--24692",
journal = "Aging",
issn = "1945-4589",
publisher = "US Administration on Aging",
number = "24",
}