Prolactin signaling drives tumorigenesis in human high grade serous ovarian cancer cells and in a spontaneous fallopian tube derived model

Subbulakshmi Karthikeyan, Angela Russo, Matthew Dean, Daniel D. Lantvit, Michael Endsley, Joanna E. Burdette

Research output: Contribution to journalArticlepeer-review

Abstract

The pathways responsible for tumorigenesis of high grade serous ovarian cancer (HGSOC) from the fallopian tube epithelium (FTE) are still poorly understood. A human prolactin (PRL) like gene, Prl2c2 was amplified >100 fold in a spontaneous model of FTE-derived ovarian cancer (MOEhigh - murine oviductal epithelium high passage). Prl2c2 stable knockdown in MOEhigh cells demonstrated a significant reduction in cell proliferation, 2-dimensional foci, anchorage independent growth, and blocked tumor formation. The overall survival of ovarian cancer patients from transcriptome analysis of 1868 samples was lower when abundant PRL and prolactin receptors (PRL-R) were expressed. A HGSOC cell line (OVCAR3) and a tumorigenic human FTE cell line (FT33-Tag-Myc) were treated with recombinant PRL and a significant increase in cellular proliferation was detected. A CRISPR/Cas9 mediated PRL-R deletion in OVCAR3 and FT33-Tag-Myc cells demonstrated significant reduction in cell proliferation and eliminated tumor growth using the OVCAR3 model. PRL was found to phosphorylate STAT5, m-TOR and ERK in ovarian cancer cells. This study identified Prl2c2 as a driver of tumorigenesis in a spontaneous model and confirmed that prolactin signaling supports tumorigenesis in high grade serous ovarian cancer.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalCancer Letters
Volume433
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

Keywords

  • High grade serous ovarian cancer and p53 phosphorylation
  • Prolactin
  • Prolactin receptor
  • Spontaneous fallopian tube derived ovarian cancer model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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