Nitze, Louise Maymann2; Galsgaard, Elisabeth Douglas3; Din, Nanni3; Lund, Vibe Luja4; Rasmussen, Birgitte Bruun5; Berchtold, Martin Werner6; Christensen, Leif3; Panina, Svetlana3
1 Cell Biology and Physiology, Department of Biology, Faculty of Science, Københavns Universitet2 Biologisk Institut, Københavns Universitet3 Novo Nordisk A/S (Biz)4 Department of Anatomy and Cell Biology, University of Copenhagen5 Herlev University Hospital6 Cell Biology and Physiology, Department of Biology, Faculty of Science, Københavns Universitet
The pituitary hormone prolactin (PRL) has been implicated in tumourigenesis. Expression of PRL and its receptor (PRLR) was reported in human breast epithelium and breast cancer cells. It was suggested that PRL may act as an autocrine/paracrine growth factor. Here, we addressed the role of locally synthesised PRL in breast cancer. We analysed the expression of PRL in human breast cancer tumours using qPCR analysis and in situ hybridization (ISH). PRL mRNA expression was very low or undetectable in the majority of samples in three cDNA arrays representing samples from 144 breast cancer patients and in 13 of 14 breast cancer cell lines when analysed by qPCR. In accordance, PRL expression did not reach detectable levels in any of the 19 human breast carcinomas or 5 cell lines, which were analysed using a validated ISH protocol. Two T47D-derived breast cancer cell lines were stably transfected with PRL-expressing constructs. Conditioned medium from the T47D/PRL clones promoted proliferation of lactogen-dependent Nb2 cells and control T47D cells. Surprisingly, the PRL-producing clones themselves displayed a lower proliferation rate as compared to the control cells. Their PRLR protein level was reduced and the cells were no longer responsive to exogenous recombinant PRL. Taken together, these data strongly indicate that autocrine PRL signalling is unlikely to be a general mechanism promoting tumour growth in breast cancer patients.
Breast Cancer Research and Treatment, 2013, Vol 142, Issue 1, p. 31-44
Autocrine prolactin; Breast cancer; Ectopic expression; In situ hybridization; qPCR