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Local production of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> appears to occur also at other sites where 1\u03b1-hydroxylase is expressed for autocrine\/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1\u03b1-hydroxylated vitamin D analogues to target tissues where 1\u03b1-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1\u03b1-hydroxylase in breast cancer and to investigate whether a non-1\u03b1-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D<jats:sub>3<\/jats:sub> 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The expression of 1\u03b1-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and\/or RT-PCR. Consecutive cryosections of 6 \u03bcm essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>1\u03b1-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1\u03b1-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1\u03b1-hydroxylase, 1 \u00b1 0.07 versus 0.7 \u00b1 0.05, respectively (p &lt; 0.001); 24-hydroxylase, 1 \u00b1 0.08 verus 2.1 \u00b1 0.2, respectively (p &lt; 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 \u00b1 0.09 and 1.4 \u00b1 0.12 (p &lt; 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1\u03b1-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1\u03b1-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>These results demonstrate nearly normal expression levels of 1\u03b1-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1\u03b1-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1\u03b1-hydroxylase is expressed.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr1332","type":"journal-article","created":{"date-parts":[[2005,10,8]],"date-time":"2005-10-08T06:13:58Z","timestamp":1128752038000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["25-Hydroxyvitamin D31\u03b1-hydroxylase expression in breast cancer and use of non-1\u03b1-hydroxylated vitamin D analogue"],"prefix":"10.1186","volume":"7","author":[{"given":"Ulrika","family":"Segersten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille Kaae","family":"Holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyman","family":"Bj\u00f6rklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Hessman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Nordgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Binderup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"\u00c5kerstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Westin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,10,6]]},"reference":[{"key":"1311_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1677\/erc.0.0090045","volume":"9","author":"KW Colston","year":"2002","unstructured":"Colston KW, Hansen CM: Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. 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