The expression of retinoic acid receptors and the effects in vitro by retinoids in human pancreatic cancer cell lines.
BACKGROUND
Analogues of vitamin A have been shown to influence growth of malignant tissue, such as pancreatic cancer.


OBJECTIVE
To study the expression of retinoic acid receptors (RAR) in pancreatic cancer cells and the effect of three different retinoids on the cell number in vitro were studied.


METHODS
Cell lines were established from 13 patients who underwent surgery for pancreatic adenocarcinoma. The expression of the retinoic acid receptors (RAR) and retinoic X receptor (RXR) subtypes (alpha, beta, and gamma) was studied with western blotting and specific antibodies. The effect of incubation with all-trans-retinoic acid (atRA; tretinoin), 9-cis-retinoic acid (9-cis-RA), and 13-cis-retinoic acid (13-cis-RA; isotretinoin) on the cell number was examined with use of a Roche XTT cell proliferation kit.


RESULTS
The RXR alpha receptor was expressed in all cell lines. RAR alpha,beta and RXR beta were expressed in most of them. RXR gamma was expressed in about half of the cell lines and RAR gamma in only one. Incubation of the cells with retinoids showed a decreased cell number at concentrations of 10(4) M, except for 9-cis-RA, to which only about half of the cell lines responded.


CONCLUSIONS
Two or more of the RAR subtypes were expressed in each pancreatic cell line. There was no uniform pattern of receptor expression; however, the cell lines responded with decreased cell number to high concentrations of atRA and 13-cis-RA but not to 9-cis-RA.
Department of Surgery, Lund University, Lund, Sweden.
Elin
E
Albrechtsson
Bodil
B
Ohlsson
Jan
J
Axelson
D000230:Adenocarcinoma; D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D015474:Isotretinoin / Q000494:pharmacology; D010190:Pancreatic Neoplasms; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; D015474:Isotretinoin