Amplification of basal/stem cells in prolactin-induced prostate tumors: deciphering the mechanisms

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-134
Lucila Sackmann Sala*, Antoine Angelergues, Ivan Pourmir, Florence Boutillon, Elodie Rambaud and Vincent Goffin
Inserm U845, Paris, France
Basal/stem cells of the prostate epithelium have been implicated as the initiating cells for prostate cancer. Our previous studies have shown an amplification of these cells in mice that overexpress prolactin (PRL) in the prostate (Pb-PRL mice) (1). Thus, we set out to explore the role of local PRL on prostate carcinogenesis. Basal/stem cells of Pb-PRL and control mice were analyzed by FACS using the Lin-Sca1+CD49fhigh (LSC) markers. Consistent with our previous results, Pb-PRL mice showed a significantly higher percentage of LSC (basal/stem) cells than control mice. To test if this amplification was a direct action of PRL on basal/stem cells, we grew these cells in 3D cultures to form prostate spheres and subjected them to PRL-stimulation. No differences in sphere numbers or sizes were observed after in vitro stimulation with PRL. In addition, immunohistochemical analysis did not reveal any activation of canonical signaling pathways (pSTAT5, pSTAT3, pERK) in prostate spheres after PRL-stimulation. Moreover, preliminary mRNA expression data suggests that the PRL receptor is not present on sorted prostate basal/stem cells. Together, these data indicate that the amplification of prostate basal/stem cells might not be due to a direct action of PRL on these cells. Rather, PRL could activate other paracrine signals in luminal or stromal cells, which in turn could cause the observed amplification of basal/stem cells. We have now started to evaluate several candidate signaling pathways to test this hypothesis.

(1) Rouet V et al. Proc Natl Acad Sci USA 2010; 107:15199.

Nothing to Disclose: LS, AA, IP, FB, ER, VG

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by the Fondation ARC pour la Recherche sur le Cancer (grant SFI20101201635) and by the Fondation de France (grant 2011-00020359). LSS is supported by a post-doctoral fellowship from Fondation ARC (PDF20101202327).