Progesterone receptor isoform-dependent cross-talk between prolactin and fatty acid synthase in breast cancer

Javier A. Menendez, Susan K. Peirce, Adriana Papadimitropoulou, Elisabet Cuyàs, Travis Vander Steen, Sara Verdura, Luciano Vellon, Wen Y. Chen, Ruth Lupu

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish (US)
Pages (from-to)24671-24692
Number of pages22
JournalAging
Volume12
Issue number24
DOIs
StatePublished - Dec 31 2020

Keywords

  • G129R
  • endocrine therapy
  • luminal breast cancer
  • prolactin receptor
  • prolactin receptor

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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