Prolactin Regulation of Cell Proliferation and Apoptosis

Buckley, Arthur R.

doi:10.1007/978-1-4615-1683-5_13

Cited by 2 publications

(2 citation statements)

References 115 publications

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“…This PRL-induced increase in cell turnover is further evidence of distinct activities of these two factors. The apparent inability of PRL to promote survival in vivo is consistent with the similar level of apoptosis in transplanted PRL ϩ/ϩ and PRL Ϫ/Ϫ epithelium 47 but differs from effects observed in vitro, 1,48 underscoring the importance of in vivo studies.…”

Section: Discussionsupporting

confidence: 59%

Prolactin Potentiates Transforming Growth Factor α Induction of Mammary Neoplasia in Transgenic Mice

Arendt

Rose-Hellekant

Sandgren

et al. 2006

The American Journal of Pathology

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Prolactin influences mammary development and carcinogenesis through endocrine and autocrine/paracrine mechanisms. In virgin female mice, pro-lactin overexpression under control of a mammary selective nonhormonally responsive promoter, neu-related lipocalin, results in estrogen receptor alpha (ERalpha)-positive and ERalpha-negative adenocarcinomas. However, disease in vivo occurs in the context of dysregulation of multiple pathways. In this study, we investigated the ability of prolactin to modulate carcinogenesis when co-expressed with the potent oncogene transforming growth factor alpha (TGFalpha) in bitransgenic mice. Prolactin and TGFalpha cooperated to reduce dramatically the latency of mammary macrocyst development, the principal lesion type induced by TGFalpha. In combination, prolactin and TGFalpha also increased the incidence and reduced the latency of other preneoplastic lesions and increased cellular turnover in structurally normal alveoli and ducts compared with single transgenic females. Bitransgenic glands contained higher levels of phosphorylated ERK1/2 compared with single TGFalpha transgenic glands, suggesting that this kinase may be a point of signaling crosstalk. Furthermore, transgenic prolactin also reversed the decrease in ERalpha induced by neu-related lipocalin-TGFalpha. Our findings demonstrate that locally produced prolactin can strikingly potentiate the carcinogenic actions of another oncogene and modify ovarian hormone responsiveness, suggesting that prolactin signaling may be a potential therapeutic target.

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Section: Discussionsupporting

confidence: 59%

Prolactin Potentiates Transforming Growth Factor α Induction of Mammary Neoplasia in Transgenic Mice

Arendt

Rose-Hellekant

Sandgren

et al. 2006

The American Journal of Pathology

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“…PRL exerts trophic effects on many of these targets, promoting proliferation (for review, Buckley, 2001). Although the mechanism that mediates this action of PRL has not been elucidated for many of these systems, PRL has been shown to increase transcription of members of the cyclin D family in some cell types (Brockman et al, 2002;Friedrichsen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter

Brockman

Schuler

2005

Molecular and Cellular Endocrinology

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Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G, phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning −254 to −180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the −254 to −180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.

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Prolactin Regulation of Cell Proliferation and Apoptosis

Cited by 2 publications

References 115 publications

Prolactin Potentiates Transforming Growth Factor α Induction of Mammary Neoplasia in Transgenic Mice

Prolactin Potentiates Transforming Growth Factor α Induction of Mammary Neoplasia in Transgenic Mice

Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter

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