Impaired turnover of prolactin receptor contributes to transformation of human breast cells

Abstract

Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr).

PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the betaTrcp E3 ubiquitin ligase and facilitates PRLr degradation.

Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription.

Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth.

Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells.

Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.

 

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See also:

- The Di Bella Method (A Fixed Part - Bromocriptine/Cabergoline);

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.