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Breast cancer and Vitamin D receptors, CP27B1, and CYP24A1 – Sept 2010

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

BMC Cancer 2010, 10:483 doi:10.1186/1471-2407-10-483
Nair Lopes (nlopes@ipatimup.pt) Barbara Sousa (bsousa@ipatimup.pt) Diana Martins (dianam@ipatimup.pt) Madalena Gomes (mgomes@ipatimup.pt) Daniella Vieira (daniellavieira.hu@gmail.com) Luiz A Veronese (lveronese@terra.com.br) Fernanda Milanezi (mmilanezi@ipatimup.pt) Joana Paredes (jparedes@ipatimup.pt)
Jose L Costa (jcosta@ipatimup.pt) Fernando Schmitt (fschmitt@ipatimup.pt)
Publication date 11 September 2010
Nair Lopes1, Barbara Sousa1, Diana Martins1, Madalena Gomes1, Daniella Vieira2, Luiz A Veronese3, Fernanda Milanezi1, Joana Paredes1, Jose L Costa1, Fernando Schmitt1, 4
1 IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto (Rua Dr Roberto Frias, s/n), Porto (4200-465), Portugal
2 Department of Pathology, Federal University of Santa Catarina (Campus Reitor Joao David Ferreira Lima), Florianopolis (88040-970), Brazil
3 Department of Pathology, General Hospital of UNIMED (Rua Gaspar de Lemos, 2), Aracatuba
(16013-800), Brazil
4 Medical Faculty of the University of Porto (Alameda Prof. Hernani Monteiro), Porto (4200-319), Portugal
Corresponding author: Fernando Schmitt, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Tel: +351 225570700; Fax: +351 225570799; E-mail: fschmitt at ipatimup.pt
Running title: Vitamin D pathways unbalanced in breast lesions
Keywords: Vitamin D, VDR, CYP27B1, CYP24A1, breast cancer
NL (nlopes@ipatimup.pt)
BS (bsousa@ipatimup.pt)
DM (dianam@ipatimup.pt)
MG (mgomes@ipatimup.pt)
DV (daniellavieira.hu@gmail.com)
LAV (lveronese@terra.com.br)
1 Fernanda Milanezi (mmilanezi@ipatimup.pt) Joana Paredes (jparedes@ipatimup.pt) Jose L Costa (jcosta@ipatimup.pt) Fernando Schmitt (fschmitt@ipatimup.pt)

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.

Figure 2 from PDF attached at the bottom of this page
Image


See also VitaminDWiki

Attached files

ID Name Comment Uploaded Size Downloads
764 Genes breast cancer and vitamin D receptor - Sept 2010.PDF PDF admin 26 Sep, 2011 21:28 789.01 Kb 737
763 Breast cancer Vitamin D receptors etc.png admin 26 Sep, 2011 21:27 33.09 Kb 1553
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