Prolactin Overexpression by MDA-MB-435 Human Breast Cancer Cells Accelerates Tumor Growth

Liby, Karen T.; Neltner, Bonnie; Mohamet, Lisa; Menchen, Lindsey; Ben‐Jonathan, Nira

doi:10.1023/a:1023956223037

Cited by 76 publications

(61 citation statements)

References 42 publications

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“…Now, these data need to be validated using human cell xenograft approaches, as these two novel mechanisms seem to be more specific to this species. Although PRL-transfected breast cancer cells have been used in the past to demonstrate the growth-promoting effect of locally over-expressed PRL in xenografts (Liby et al 2003), there is currently no unified cell model used for targeting autocrine/paracrine PRL actions at preclinical stages of therapeutic molecule development. This is even more true for PRLR-I146L, which is yet to be identified in any cell line classically used in PRL biology.…”

Section: Discussionmentioning

confidence: 99%

New concepts in prolactin biology

Bernichtein

Touraine²,

Goffin³

2010

Journal of Endocrinology

154

112

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Human prolactin (PRL) is currently viewed as a hormone of pituitary origin, whose production (i.e. serum levels) is controlled by dopamine, whose biological actions relate exclusively to lactation and reproductive functions, for which any genetic disorder is yet to be identified, and whose unique associated pathology is hyperprolactinemia. Both experimental studies and human sample/cohort-based investigations performed during the past decade have considerably widened our perception of PRL biology: i) there are now strong epidemiological arguments supporting the fact that circulating PRL is a risk factor for breast cancer, ii) in addition to the endocrine hormone, locally produced PRL has been documented in several human tissues; there is increasing evidence supporting the tumor growth potency of local PRL, acting via autocrine/paracrine mechanisms, in both rodent models, and human breast and prostate tumors, iii) the first functional germinal polymorphisms of the PRL receptor were recently identified in patients presenting with breast tumors, which involve single amino acid substitution variants exhibiting constitutive activity, iv) human PRL analogs have been engineered, which were shown in experimental models to down-regulate the effects triggered by local PRL (competitive antagonism) or by the constitutively active receptor variants (inverse agonism). The aim of this review is to discuss these novel concepts in PRL biology, including their potential pathophysiological outcomes.

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Section: Discussionmentioning

confidence: 99%

New concepts in prolactin biology

Bernichtein

Touraine²,

Goffin³

2010

Journal of Endocrinology

154

112

View full text Add to dashboard Cite

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“…PRL levels were determined by a cell-based bioassay as described in ref. 18. SDS/ PAGE and Coomassie blue staining of WAPs in the milk of lactating ER␣ fl/fl (ϩ/ϩ) and WAP-ERKO (Ϫ/Ϫ) females were performed as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Estrogen receptor-α expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice

Feng

Manka

Wagner

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

238

181

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The estrogen receptor-␣ (ER␣) is a critical transcription factor that regulates epithelial cell proliferation and ductal morphogenesis during postnatal mammary gland development. Tissue recombination and transplantation studies using the first generation of ER␣ knockout (ERKO) mice suggested that this steroid hormone receptor is required in the mammary stroma that subsequently exerts its effect on the epithelium through additional paracrine signaling events. A more detailed analysis revealed that ERKO mice produce a truncated ER␣ protein with detectable transactivation activity, and it is likely that this functional ER␣ variant has masked the biological significance of this steroid receptor in the mammary epithelium. In this article, we describe the generation a Cre-loxbased conditional knockout of the ER␣ gene to study the biological function of this steroid receptor in the epithelial compartment at defined stages of mammary gland development. The mouse mammary tumor virus (MMTV)-Cre-mediated, epithelial-specific ablation of exon 3 of the ER␣ gene in virgin mice severely impaired ductal elongation and side branching. The conditional knockout resulted in ablation of the ER␣ protein, and the progesterone receptor (PR), whose expression is under the control of ER␣, was largely absent. The whey acidic protein (WAP)-Cre-mediated deletion of ER␣ during successive gestation cycles resulted in a loss of ductal side-branching and lobuloalveolar structures, ductal dilation, and decreased proliferation of alveolar progenitors. These abnormalities compromised milk production and led to malnourishment of the offspring by the second lactation. These observations suggest that ER␣ expression in the mammary epithelium is essential for normal ductal morphogenesis during puberty and alveologenesis during pregnancy and lactation.conditional knockout ͉ mammary gland

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“…Most of these genes have roles in promoting cell proliferation or progression through the cell cycle. Both PRL (prolactin) and EDN1 (endothelin 1) encode secreted proteins known to promote cell proliferation [15,16]. Endogenously expressed prolactin has been demonstrated to protect established breast cancer cell lines from ceramide-dependent apoptosis [17], a pathway invoked by many chemotherapy drugs [18].…”

Section: Cell Cycle Regulation/cell Proliferationmentioning

confidence: 99%