Hyperprolactinemia is an indicator of progressive disease and poor prognosis in advanced breast cancer

Holtkamp, W.; Nagel, G. A.; Wander, H.-E.; Rauschecker, H.; Heyden, D. von

doi:10.1002/ijc.2910340307

Cited by 77 publications

(42 citation statements)

References 18 publications

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“…Increased expression of GH with respect to normal mammary gland has been associated with proliferative disorders, including invasive ductal carcinoma (46). In the case of PRL, it has been reported that as many as 44% of patients with metastatic breast disease have been hyperprolactinaemic at some stage during the course of the disease (47), and the presence of bioactive PRL in human breast cancer cells acts in an autocrine manner to stimulate cell proliferation (48). Transgenic mice have been used to study the effects of high concentrations of human GH and PRL.…”

Section: Discussionmentioning

confidence: 99%

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Gil¹,

Seoane²,

Blanco³

et al. 2005

eur j endocrinol

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Background: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported. Objective: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation. Methods: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine. Results: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation. Conclusions: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.

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Section: Discussionmentioning

confidence: 99%

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Gil¹,

Seoane²,

Blanco³

et al. 2005

eur j endocrinol

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“…PRL levels above 12.6 ng/ml were linked to a poor survival prognosis in postmenopausal subjects who had undergone mastectomy for breast cancer (Wang et al, 1995). Plasma PRL levels above 32 ng/ml were seen in 8% of 149 women with metastatic breast cancer, in contrast to none of the 221 control subjects (po0.001) (Holtkamp et al, 1984). In the same study, mean survival time after mastectomy in the group with normal PRL was 154 months, compared with 89 months in the hyperprolactinemic group.…”

Section: Breast Cancermentioning

confidence: 98%

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Emiliano

Fudge

2004

Neuropsychopharmacol

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The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon.

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“…It has also been demonstrated that hyperprolactinemia is associated with metastatic disease among certain breast cancer patients. Hyperprolactinemia has been suggested to be an indicator of the progression of the disease supported by ®ndings that PRL levels decrease if remission is achieved (Holtkamp et al, 1984).…”

Section: Humansmentioning

confidence: 99%

The role of prolactin and growth hormone in breast cancer

Wennbo

Törnell

2000

Oncogene

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This review will focus on the role for prolactin (PRL) and growth hormone (GH) in mammary tumor formation. Much attention has previously been focused on circulating levels of GH/PRL in relation to mammary tumor formation. We will review data demonstrating that these ligands also could be produced locally in dierent organs, including the mammary gland and mammary tumors, and suggest that this local production may be of importance for pathological conditions. We will also discuss mechanisms for crosstalk between steroids and GH/PRL. A crosstalk between GH-and PRL response is possible at multiple levels. In the human, GH can activate both the prolactin receptor (PRLR) and the growth hormone receptor (GHR). We have demonstrated that activation of the PRLR, but not the GHR, is inducing mammary tumors in transgenic mice. Furthermore, the elevated levels of insulin-like growth factor 1 (IGF-I) seen in the GHR activating transgenic mice is not sucient for tumor induction. The induced tumors express functionally active prolactin that could be of importance for the tumor formation. Paracrine/aurocrine stimulation by PRL may be more important than PRL transported via the circulation. In women, the role for stimulation of the PRLR and/or the GHR in mammary tumor formation has not been proven, although experiments from primates suggest that the PRLR could be of importance.

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Hyperprolactinemia is an indicator of progressive disease and poor prognosis in advanced breast cancer

Cited by 77 publications

References 18 publications

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

The role of prolactin and growth hormone in breast cancer

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