A mimic of phosphorylated prolactin inhibits human breast cancer cell proliferation via upregulation of p21 waf1

Abstract

A mimic of phosphorylated prolactin (S179D PRL) inhibits mouse normal mammary HC11 cell proliferation through the upregulation of the vitamin D receptor (VDR) and p21.

Here, we investigated whether S179D PRL also inhibited growth of human breast cancer MCF7 cells via VDR and p21.

Western blots showed that S179D PRL upregulated VDR and p21 after the cells were incubated with S179D PRL for 3 days.

These effects were blocked by the MAP kinase blocker PD98059 (25 μM), indicating that MAPK plays a role in VDR and p21 upregulation.

To confirm whether VDR contributes to p21 upregulation, we used two constructs that express luciferase. One (p21 VDRE Luc) has the vitamin D response element (VDRE) in the p21 promoter region; the other (p21 NO-VDRE Luc) does not.

The results show that S179D PRL upregulated p21 VDRE Luc activity in p21 VDRE Luc-transfected cells more than in p21 NO-VDRE-transfected cells, indicating that S179D PRL upregulated p21 via VDR.

A cell proliferation assay showed that S179D PRL inhibits cell proliferation in a dose-dependent manner.

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See also:

- Official Web Site: The Di Bella Method;

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

- 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 - 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);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

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

- 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;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

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