Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Expression of Vitamin D receptor and 24-hydroxylase genes in breast cancer

MLH Katayama MSc 2, EM Barbosa MD PhD 1, MM Brentani PhD

Instituto Brasileiro do Controle do Cancer, 1 Faculdade de Medicina da USP, Disciplina de Oncologia Depto de Radiologia, 2 São Paulo, Brazil,

AIMS: We have determined the vitamin D receptor (VDR) mRNA by Northern analysis in tumor and normal adjacent tissue samples obtained from 50 breast cancer patients. METHODS: VDR mRNA (4,6 Kb) was expressed by 96% of the tumors and normal tissues. The mean VDR mRNA relative levels in tumor and normal tissue were respectively 9.1 „b 25.6 and 7.9„b18.3 but the distribution of values was not statistically different. The individual mRNA levels in tumor and normal tissue showed parallel variation (r = 0,93 p < 0001). VDR protein was also determined by immunohistochemistry utilizing the VD2F12 monoclonal antibody and the index of antigen positivity was not discrepant from mRNA determination. VDR mRNA values were classified considering the mean relative values as a cut off and compared to clinical prognostic factors (age, ER and PR, number of lymphnodes, staging and tumor size), no statistical associations were found. RESULTS: Expression of 24-hydroxylase mRNA also analyzed by Northern was not detected in the tumors, as well in the normal tissues. Treatment of the mouse mammary normal cells HC11 with 1,25(OH)2D3 10-7M induced growth arrest but no evidence was found for induction of 24-hydroxylase. Ras transfected HC11 cells showed decreased VDR mRNA levels and was resistant to the growth inhibiting effect of 1,25(OH)2D3, but expressed 24-hydroxylase mRNA constitutively. CONCLUSIONS: 1) VDR mRNA levels of normal breast tissue are maintained in breast tumors 2) Although detected in some breast cell lines, the 1,25(OH)2D3 down catabolic 24-hydroxylase pathway did not occur generally in breast tissue.

KEY WORDS: Breast cancer, VDRmRNA, 24-Hydroxylase mRNA, Breast neoplasms, Receptors, calciferol, Steroid hydroxylases.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic risk assessment.