Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis
- CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)
- IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal)
- Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD) (Portugal)
Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[α]anthracene (DMBA). Carcinogen-induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer is associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg-RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. - Highlights: • RGN immunoreactivity was negatively correlated with breast cancer differentiation. • Transgenic overexpression of RGN diminished incidence of carcinogen-induced tumors. • Transgenic overexpression of RGN restricted proliferation and fostered apoptosis. • RGN has a protective role in the carcinogenesis of mammary gland.
- OSTI ID:
- 22416973
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 330; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
Similar Records
CHL1 is involved in human breast tumorigenesis and progression
PSME3 induces epithelial–mesenchymal transition with inducing the expression of CSC markers and immunosuppression in breast cancer