Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop

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Published on Tuesday, 26 December 2017

Abstract

The neuroendocrine hormone prolactin is a growth factor required for the proliferation and terminal differentiation of the human breast.

These effects are mediated by the prolactin receptor, a member of the growth factor receptor family.

Three prolactin receptor isoforms (long, intermediate, and short) have been identified in the rat, which differ in the length of their intracytoplasmic domains. In humans, however, only the long prolactin receptor isoform had been identified previously. The expression of the human intermediate prolactin receptor is demonstrated and preliminary evidence for a human short isoform is presented.

Heterogeneous expression of prolactin receptor, at the immunoblot and immunohistochemical levels was observed in breast carcinoma specimens.

A statistically significant correlation between prolactin receptor and estrogen receptor expression was noted.

An autocrine/paracrine role for prolactin within breast tissues was further examined by performing reverse transcription polymerase chain reaction on RNA isolated from cell lines and clinical specimens with prolactin-specific primers. A 585-bp product was observed and found to be identical to human prolactin.

The synthesis of prolactin by breast epithelium was confirmed by in situ hybridization analysis of breast tissues and the detection of bio- and immunoreactive prolactin in breast cancer lines.

These analyses indicate that the principal site for prolactin expression within the normal or malignant breast residues within the epithelium.

These data indicate that prolactin may participate in an autocrine/paracrine stimulatory loop within breast tissues and suggest a role for this growth factor in the pathogenesis of breast cancer.

 



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

- The Di Bella Method (A Fixed Part - Vitamin C/Ascorbic Acid, 2–4 grams, twice a day orally);

- The Di Bella Method (A Variable Part - Selenium methonine, 40 μg capsules, twice a day);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);


 


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- 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;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

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