Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity.
AffiliationBreast Biology Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. SHowell@picr.man.ac.uk
MetadataShow full item record
AbstractINTRODUCTION: Exogenous prolactin is mitogenic and antiapoptotic in breast cancer cells, and overexpression of autocrine prolactin cDNA in breast cancer cell lines has been shown to stimulate their growth and to protect against chemotherapy-induced apoptosis. We examined the effects of the 'pure' prolactin receptor antagonist Delta1-9-G129R-hPrl (Delta1-9) on the breast cancer cell number and clonogenicity, alone and in combination with chemotherapy. METHODS: The effects of doxorubicin, paclitaxel and Delta1-9 on the growth of breast cancer cell lines (MCF-7, T47D, MDA-MB-453, MDA-MB-468 and SK-BR-3) in monolayer culture were assessed by the sulphorhodamine B assay. Effects on clonogenicity were assessed by soft agar assay for the cell lines and by the mammosphere assay for disaggregated primary ductal carcinoma in situ samples. Dual-fluorescence immunocytochemistry was used to identify subpopulations of cells expressing the prolactin receptor and autocrine prolactin. RESULTS: Delta1-9 as a single agent had no effect on the cell number in monolayer culture, but potentiated the cytotoxic effects of doxorubicin and paclitaxel. Doxorubicin accordingly induced expression of prolactin mRNA and protein in all five breast cancer cell lines tested. Delta1-9 alone inhibited the clonogenicity in soft agar of cell lines by ~90% and the mammosphere forming efficiency of six disaggregated primary ductal carcinoma in situ samples by a median of 56% (range 32% to 88%). Subpopulations of cells could be identified in the cell lines based on the prolactin receptor and prolactin expression. CONCLUSION: Autocrine prolactin appears to act as an inducible survival factor in a clonogenic subpopulation of breast cancer cells. The rational combination of cytotoxics and Delta1-9 may therefore improve outcomes in breast cancer therapy by targeting this cell population.
CitationProlactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity. 2008, 10 (4):R68 Breast Cancer Res.
JournalBreast Cancer Research
- The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines.
- Authors: Pledgie-Tracy A, Billam M, Hacker A, Sobolewski MD, Woster PM, Zhang Z, Casero RA, Davidson NE
- Issue date: 2010 May
- Alpha(2)-adrenoceptor agonists trigger prolactin signaling in breast cancer cells.
- Authors: Castillo LF, Rivero EM, Goffin V, Lüthy IA
- Issue date: 2017 Jun
- Methotrexate, paclitaxel, and doxorubicin radiosensitize HER2-amplified human breast cancer cells to the Auger electron-emitting radiotherapeutic agent (111)In-NLS-trastuzumab.
- Authors: Costantini DL, Villani DF, Vallis KA, Reilly RM
- Issue date: 2010 Mar
- Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells.
- Authors: Kim R, Tanabe K, Emi M, Uchida Y, Toge T
- Issue date: 2003 Nov-Dec
- Reevaluation of the proposed autocrine proliferative function of prolactin in breast cancer.
- Authors: Nitze LM, Galsgaard ED, Din N, Lund VL, Rasmussen BB, Berchtold MW, Christensen L, Panina S
- Issue date: 2013 Nov