The regucalcin protein as a protective molecule in mammary gland carcinogenesis

Previous studies of the research group led by Professor Silvia Socorro demonstrated that regucalcin (RGN), a calcium-binding protein involved in the regulation of intracellular calcium and several signaling pathways, is under-expressed in breast cancer cases comparatively with non-neoplastic tissues. In the present study, published in the Experimental Cell Research journal, the same investigators from the Health Sciences Research Center, University of Beira Interior (CICS-UBI) identified RGN as a protective molecule in the carcinogenesis of mammary gland. Transgenic rats overexpressing the RGN protein showed a marked resistance to development of pharmacologically-induced mammary gland tumors and displayed a significantly lower number of invasive tumors comparatively to control animals. The differences between control and transgenic animals seem to be associated with the effects of RGN in the suppression of proliferation and regulation of apoptosis in breast cells. It was also shown that the progression of human breast infiltrating ductal carcinoma is accompanied by a decreased of RGN levels.

Authors and Affiliations:

Ricardo Marques^a, Cátia V. Vaza, Cláudio J. Maia^a, Madalena Gomes^b, Adelina Gama^c, Gilberto Alves^a, Cecília R. Santos^a, Fernando Schmitt^b,d,e,f, Sílvia Socorro^a

^a CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

^b IPATIMUP – Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

^c Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), Portugal

^d Medical Faculty, University of Porto, Porto, Portugal

^e Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada

^f Department of Pathology, University Health Network, Toronto, Canada

Abstract:

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.

Journal: Experimental Cell Research

Link: http://www.sciencedirect.com/science/article/pii/S0014482714003358