1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells

Abstract

Transforming growth factor beta s (TGF-beta s) are a family of polypeptide growth factors that regulate cellular growth, phenotype, and differentiation.

TGF-beta s are synthesized as latent high molecular weight complexes that include the NH2-terminal remnant of the TGF-beta precursor (latency-associated protein) and, frequently, latent TGF-beta binding protein. After activation, TGF-beta s act as local mediators of hormonal responses in target tissues. TGF-beta functions as a negative growth regulator for both breast cancer cells and normal mammary epithelial cells.

Vitamin D3 is growth inhibitory for the estrogen receptor-negative breast cancer cell line BT-20 and regulates TGF-beta expression in cultured keratinocytes.

We studied here the effects of vitamin D3 and its analogues on TGF-beta expression and activity in BT-20 cells. It was found that vitamin D3 enhanced both TGF-beta 1 mRNA and secretion of the protein in a time- and dose-dependent manner.

Analyses of the vitamin D3 responses in the presence of cycloheximide or actinomycin D indicated that the TGF-beta 1 mRNA induction was dependent on both protein and RNA synthesis. The amounts of latent TGF-beta binding protein were also increased in the conditioned medium but not in the pericellular matrix of vitamin D3-treated cultures. The amounts of active TGF-beta were enhanced in vitamin D3-treated cultures as well, suggesting autocrine or paracrine functions for the secreted growth factor. Some analogues of vitamin D3 (EB 1089, MC 903, and KH 1060) that are known to be potent inhibitors of breast cancer cell growth both in vitro and in vivo had similar or more pronounced inducing effects on TGF-beta 1 mRNA levels.

The present results indicate that vitamin D3 and its analogues are potent inducers of both active and latent forms of TGF-beta 1 in BT-20 breast carcinoma cells and provide evidence for coordinated regulation of latent TGF-beta binding protein and TGF-beta 1.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Calcium, 2 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);

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

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

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

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- 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;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

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- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.