Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

BMC Cancer - Tập 10 Số 1 - 2010
Nair Lopes1, Bárbara Sousa1, Diana Martins1, Mónica Gomes1, Daniella Serafim Couto Vieira2, Luiz Alberto Veronese3, Fernanda Milanezi1, Joana Paredes1, José Luís Costa1, Fernando Schmitt4
1IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto (Rua Dr Roberto Frias, s/n), Porto, (4200-465), Portugal
2Department of Pathology, Federal University of Santa Catarina (Campus Reitor João David Ferreira Lima), Florianópolis, (88040-970), Brazil
3Department of Pathology, General Hospital of UNIMED (Rua Gaspar de Lemos, 2), Araçatuba, (16013-800), Brazil
4Medical Faculty of the University of Porto (Alameda Prof. Hernâni Monteiro), Porto, (4200-319), Portugal

Tóm tắt

Abstract Background Breast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions. Methods We have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry. Results The results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%). Conclusions From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone.

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BMC Cancer

Tập 10 Số 1

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