Abstract | PURPOSE: METHODS:
Paraffin-embedded breast tissues were analyzed by immunohistochemistry (IHC). BCa progression markers in human MCF-7 and T47D BCa cell lines treated with NO donor SIN-1 or PRL, ±CPD inhibitors were analyzed by RT-qPCR and immunoblotting. RESULTS: IHC showed progressive increases in CPD, NT, Ki67, and Cullin-3 from low levels in benign tissues to high levels in ductal carcinoma in situ, low-grade, high-grade, and triple-negative BCa. CPD and NT staining were closely associated, implicating CPD in NO production. Phospho-Stat5a increased significantly from benign to high-grade BCa and was mostly nuclear. AR and PRLR were abundant in benign breast and BCa, including triple-negative tumors. SIN-1 and PRL increased VEGF-C and Runx2, but not Cullin-3, in BCa cell lines. PRL induction of VEGF-C and Runx2 was inhibited partly by CPD inhibitors, implicating NO, produced by PRL-regulated CPD, in BCa progression. CONCLUSIONS: The CPD-Arg-NO pathway contributes to BCa progression in vitro and in vivo. PRL/ androgen activation of the pathway support combined AR and PRLR blockade as an additional therapy for BCa.
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Authors | Lynn N Thomas, Emily R Chedrawe, Penelope J Barnes, Catherine K L Too |
Journal | Breast cancer research and treatment
(Breast Cancer Res Treat)
Vol. 164
Issue 1
Pg. 27-40
(Jul 2017)
ISSN: 1573-7217 [Electronic] Netherlands |
PMID | 28364216
(Publication Type: Journal Article)
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Chemical References |
- Androgens
- CUL3 protein, human
- Core Binding Factor Alpha 1 Subunit
- Cullin Proteins
- Ki-67 Antigen
- RUNX2 protein, human
- Receptors, Androgen
- Receptors, Prolactin
- Vascular Endothelial Growth Factor C
- Nitric Oxide
- 3-nitrotyrosine
- Tyrosine
- Estradiol
- Prolactin
- Carboxypeptidases
- carboxypeptidase D
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Topics |
- Androgens
(metabolism)
- Breast Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Carboxypeptidases
(antagonists & inhibitors, genetics)
- Core Binding Factor Alpha 1 Subunit
(genetics)
- Cullin Proteins
(genetics)
- Estradiol
(administration & dosage)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Ki-67 Antigen
(genetics)
- MCF-7 Cells
- Nitric Oxide
(metabolism)
- Prolactin
(metabolism)
- Receptors, Androgen
(genetics)
- Receptors, Prolactin
(genetics)
- Tyrosine
(analogs & derivatives, metabolism)
- Vascular Endothelial Growth Factor C
(genetics)
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