Prolactin increases survival and migration of ovarian cancer cells: importance of prolactin receptor type and therapeutic potential of S179D and G129R receptor antagonists

Dunyong Tan; Kuanhui E Chen; Teresa Khoo; Ameae M Walker

doi:10.1016/j.canlet.2011.06.014

Prolactin increases survival and migration of ovarian cancer cells: importance of prolactin receptor type and therapeutic potential of S179D and G129R receptor antagonists

Cancer Lett. 2011 Nov 1;310(1):101-8. doi: 10.1016/j.canlet.2011.06.014. Epub 2011 Jun 25.

Authors

Dunyong Tan¹, Kuanhui E Chen, Teresa Khoo, Ameae M Walker

Affiliation

¹ Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.

PMID: 21775057
DOI: 10.1016/j.canlet.2011.06.014

Abstract

Variably-spliced prolactin receptors (PRLRs) and PRL are expressed by the ovarian cancer cell lines, TOV-112D, OV-90 and TOV-21G. Incubation in the PRLR antagonists, G129R- or S179D-PRL, or anti-PRL reduced cell number, indicating a functional autocrine PRL growth loop. Added PRL promoted, and the antagonists decreased, cell migration. When cells were stressed, added PRL decreased apoptosis and increased survival, and the antagonists had the opposite effect. Cells expressing higher long:short PRLR ratios had increased growth, survival and migration in response to PRL. Results suggest that PRLR antagonists may be therapeutically beneficial in ovarian cancer.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Apoptosis / genetics
Blotting, Western
Cell Adhesion / drug effects
Cell Line, Tumor
Cell Movement / drug effects*
Cell Survival / drug effects
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Microscopy, Confocal
Ovarian Neoplasms / drug therapy
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Prolactin / genetics
Prolactin / metabolism
Prolactin / pharmacology*
Protein Isoforms / antagonists & inhibitors
Protein Isoforms / genetics
Protein Isoforms / metabolism
Receptors, Prolactin / antagonists & inhibitors*
Receptors, Prolactin / genetics
Receptors, Prolactin / metabolism
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction

Substances

Protein Isoforms
Receptors, Prolactin
Recombinant Proteins
prolactin, Arg(129)-
prolactin, Asp(179)-
Prolactin