Prolactin

Human prolactin (hPRL) antagonists inhibit hPRL-activated signaling pathways involved in breast cancer cell proliferation

“…Clinical treatment of these cases awaits for further development of new therapeutic approaches. Lately, the involvement of hPRL on human breast cancer is being reconsidered (Vonderhaar, 1998;Go n et al, 1999a). In this paper, we have reported that G129R-hPRL acts as an antagonist on several human breast cancer cell lines, irrespective to their ER status, suggesting that hPRL antagonists may be used in anti-estrogen insensitive breast tumors.…”

“…In the mammary gland, it participates in lobulo-alveolar development, alveolar cell growth and milk protein synthesis, acting as a proliferation and di erentiation factor (depending on the development stage). Although in rodents it has been clearly demonstrated that PRL plays a role in inducing and favoring breast cancer (Wennbo et al, 1997;Vomachka et al, 2000), its involvement in human breast neoplasia has been long debated (Vonderhaar, 1998;Go n et al, 1999a;Wennbo and Tornell, 2000). Recently, an epidemiological study has made clear the signi®cant correlation between plasma PRL levels and increased breast cancer risk in postmenopausal women (Hankinson et al, 1999).…”

“…In mammary epithelial cells (tumor and normal), PRL induces phosphorylation (and activation) of the PRLR-associated tyrosine kinase JAK2, which in turn phosphorylates latent cytoplasmic transcription factors STAT5, STAT3 and STAT1 (DaSilva et al, 1996;Schaber et al, 1998). Other pathways are also activated by PRL in mammary epithelial cells, which involve the Ras/Raf/MAP kinase (Das and Vonderhaar, 1996a,b;Schaber et al, 1998), the Protein Kinase C (Waters and Rillema, 1989;Banerjee and Vonderhaar, 1992) and the Focal Adhesion Kinase-paxillin (Canbay et al, 1997) pathways (for a review, Llovera et al, 2000). Based among others on the use of speci®c kinase inhibitors, it has been shown that the JAK/STAT and MAPK pathways play a critical role in PRL-induced proliferation of mammary epithelial cells Vonderhaar, 1996a,b, 1997).…”

Human prolactin and its antagonist, hPRL-G129R, regulate bax and bcl-2 gene expression in human breast cancer cells and transgenic mice

“…Synthesized primarily by lactotropes in the anterior pituitary, PRL is critically involved in normal mammary gland development (Nagasawa et al, 1985;Clevenger et al, 1995;Vonderhaar, 1998;Blackwell and Hammond, 1999). In addition to its role as an endocrine hormone, human PRL (hPRL) is also produced by the breast epithelium as an autocrine/paracrine growth factor, and as such functions as a cytokine (Clevenger et al, 1995(Clevenger et al, , 2003Ginsburg and Vonderhaar, 1995;BenJonathan et al, 2002).…”

Regulation of bcl-2 gene expression in human breast cancer cells by prolactin and its antagonist, hPRL-G129R

“…It is well established that hPRL is directly involved in the development and differentiation of normal mammary gland in mammalian species (Blackwell and Hammond, 1999;Clevenger et al, 1995;Nagasawa et al, 1985;Topper and Freeman, 1980;Vonderhaar, 1998). Controversy, however, still exists regarding the role of hPRL in human breast cancer.…”