Induction of differentiation by 1α-hydroxyvitamin D 5 in T47D human breast cancer cells and its interaction with vitamin D receptors

• Published in: European journal of cancer (1990) Vol. 36; no. 6; pp. 780 - 786
• Main Authors: Lazzaro, G, Agadir, A, Qing, W, Poria, M, Mehta, R.R, Moriarty, R.M, Das Gupta, T.K, Zhang, X.-K, Mehta, R.G
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.04.2000
• Subjects: Breast cancer cells; Differentiation; MCF10; T47D; Vitamin D; MCF10; T47D; Vitamin D; Differentiation; Breast cancer cells
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(00)00016-2

The role of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D 3 (1,25(OH) 2D 3), in cell differentiation is well established. However, its use as a differentiating agent in a clinical setting is precluded due to its hypercalcaemic activity. Recently, we synthesised a relatively non-calcaemic analogue of vitamin D 5, 1α-hydroxyvitamin D 5 (1α(OH)D 5), which inhibited the development of carcinogen-induced mammary lesions in culture and suppressed the incidence of chemically induced mammary carcinogmas in rats. In the present study, we determined the differentiating effects of 1α-(OH)D 5 in T47D human breast cancer cells and compared its effects with 1,25(OH) 2D 3. Cells incubated with either 10 or 100 nM of the analogues inhibited cell proliferation in a dose-dependent manner, as measured by the dimethylthiazolyl-2,5-diphenyltetrazolium bromide (MTT) assay. Similar growth-inhibitory effects were also observed for MCF10 neo cells. Both vitamin D analogues induced cell differentiation, as determined by induction of casein expression and lipid production. However, MCF10 neo cells failed to respond to either vitamin D analogue and did not undergo cell differentiation. Since the cell differentiating effect of vitamin D is considered to be mediated via the vitamin D receptor (VDR), we examined the induction of VDR using reverse transcriptase–polymerase chain reaction (RT-PCR) in both cells. The results showed that, in T47D cells, both 1,25(OH) 2D 3 and 1α(OH)D 5 induced VDR in a dose-dependent manner. Moreover, both analogues of vitamin D upregulated the expression of vitamin D response element-chloramphenicol acetyl transferase (VDRE-CAT). These results collectively indicate that 1α-(OH)D 5 may mediate its cell-differentiating action via VDR in a manner similar to that of 1,25(OH) 2D 3.