Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number.
OBJECTIVE
The vitamin D-receptor (VDR) has been detected in both normal and malignant cells of different tissues. Treatment with vitamin D(3) has been suggested as a possible therapy in malignant diseases such as pancreatic cancer. Synthetic analogues of vitamin D(3) have a less hypercalcemic effect than native vitamin D(3). The aim was to study the expression of the VDR in human pancreatic cancers and to study the in vitro effect of an analogue to vitamin D(3) on cell lines established from these cancers.


METHODS
The pancreatic cancer cell lines were established from primary cultures with only cancer cells. A probe specific for the human VDR was used. After reverse-transcriptase PCR and Northern blotting, the expression of the VDR in normal pancreas and in pancreatic cancers was compared. The cell lines were incubated with EB 1089, a synthetic analogue vitamin of D(3), in dose-response studies. The cell number was measured by the XTT colorimetric method.


RESULTS
The VDR was expressed in all cancers and in six of the cell lines the expression was increased more than 3-fold compared to normal pancreas. All cell lines developed from human pancreatic cancers responded with a decreased cell number to the vitamin D(3) analogue at concentrations of 10(-5) M or higher.


CONCLUSIONS
The VDR was expressed in all pancreatic cancers studied. Cell lines derived from these cancers responded with a decrease in cell number to high concentrations of a vitamin D(3) analogue. These results, and the doses to use, have to be confirmed with in vivo studies.
Albrechtsson
Elin
E
Department of Surgery, Lund University, Sweden.
Jonsson
Tord
T
Möller
Sebastian
S
Höglund
Mattias
M
Ohlsson
Bodil
B
Axelson
Jan
J
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; C078903:seocalcitol