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

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Lopes, N (Author) Other; Sousa, B (Author) Other; Martins, D (Author) Other; Gomes, M (Author) Other; Vieira, D (Author) Other; Veronese, LA (Author) Other; Milanezi, F (Author) Other; Joana Paredes (Author) FMUP; Costa, JL (Author) Other; Fernando Schmitt (Author) FMUP

Journal

Title: BMC Cancer

Vol. 10

Final page: 483

ISSN: 1471-2407

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 160 Citations

Scopus - 180 Citations

Other information

Authenticus ID: P-003-2WK

DOI: 10.1186/1471-2407-10-483

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10