Vitamin D and prostate cancer
| Autor: | Pekka Vilja, Yan-Ru Lou, T Hasan, Susanna Miettinen, Timo Ylikomi, Pasi Pennanen, N Aksenov, P Pasanen, Pentti Tuohimaa, Merja Bläuer, Heimo Syvälä, Alex Lyakhovich, Tommi Manninen, Merja H. Ahonen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Fibroblast Growth Factor 7 Endocrinology Diabetes and Metabolism Clinical Biochemistry Biochemistry Calcitriol receptor vitamin D deficiency Prostate cancer Endocrinology Cytochrome P-450 Enzyme System Prostate Internal medicine Tumor Cells Cultured medicine Vitamin D and neurology Animals Humans Amino Acid Sequence RNA Messenger Vitamin D Vitamin D3 24-Hydroxylase Molecular Biology DNA Primers Cancer prevention Base Sequence business.industry Prostatic Neoplasms Cancer Cell Biology Middle Aged Vitamin D Deficiency medicine.disease Immunohistochemistry Rats Fibroblast Growth Factors Gene Expression Regulation Neoplastic Androgen receptor medicine.anatomical_structure Steroid Hydroxylases Cholestanetriol 26-Monooxygenase Molecular Medicine Mitogen-Activated Protein Kinases business |
| Zdroj: | University of Helsinki |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/s0960-0760(00)00141-2 |
| Popis: | Our recent epidemiological study (Ahonen et al., Cancer Causes Control 11(2000) (847-852)) suggests that vitamin D deficiency may increase the risk of initiation and progression of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19000 middle-aged men free of clinically verified prostate cancer. More than one-half of the serum samples had 25OH-vitamin D (25-VD) levels below 50 nmol/l, suggesting VD deficiency. Prostate cancer risk was highest among the group of younger men (40-51 years) with low serum 25-VD, whereas low serum 25-VD appeared not to increase the risk of prostate cancer in older men (>51 years). This suggests that VD has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25-VD concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25-VD levels delayed the appearance of clinically verified prostate cancer by 1.8 years. Since these results suggest that vitamin D has a protective role against prostate cancer, we tried to determine whether full spectrum lighting (FSL) during working hours could increase serum 25-VD concentrations. After 1-month exposure, there was no significant increase in the serum 25-VD level, although there was a bias towards slightly increasing values in the test group as opposed to decreasing values in controls. There was no significant change in the skin urocanic acid production. The possibility to use FSL in cancer prevention is discussed. In order to clarify the mechanism of VD action on cell proliferation and differentiation, we performed studies with the rat and human prostates as well prostate cancer cell lines. It is possible that 25-VD may have a direct role in the host anticancer defence activity, but the metabolism of vitamin D in the prostate may also play an important role in its action. We raised antibodies against human 1alpha-hydroxylase and 24-hydroxylase. Our preliminary results suggest that vitamin D is actively metabolised in the prostate. Vitamin D appears to upregulate androgen receptor expression, whereas androgens seem to upregulate vitamin D receptor (VDR). This may at least partially explain the androgen dependence of VD action. VD alone or administered with androgen causes a suppression of epithelial cell proliferation. VD can activate mitogen-activated kinases, erk-1 and erk-2, within minutes and p38 within hours. Also, auto/paracrine regulation might be involved, since keratinocyte growth factor (mRNA and protein) was clearly induced by VD. Based on these studies, a putative model for VD action on cell proliferation and differentiation is presented. |
| Databáze: | OpenAIRE |
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