Differential expression of estrogen receptors-, vitamin D receptor- and 1 -hydroxylase 25- hydroxy vitamin D mRNA in human normal thyroid vs. papillary carcinoma cells is linked to differential effects of estrogen and vitamin D on cell growth

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 459-496-Thyroid Neoplasia & Case Reports
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-462
Asaf Aizic1, Dalia Somjen*1, Elena Izkhakov2, Orli Sharon1, Ester Knoll3, F Kohen4, Rona Limor1, Dan Fliss1 and Naftali Stern5
1Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 2Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University,, 4Weizmann Institute of Science, Rehovot, Israel, 5Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Differential expression of estrogen receptors-, vitamin D receptor- and 1a -hydroxylase 25- hydroxy vitamin D mRNA in human normal thyroid vs. papillary carcinoma cells is linked to differential effects of estrogen and vitamin D on cell growth  

 

D. Somjen, E. Izkhakov, O.Sharon, E. Knoll, F. Kohen, A. Aizic*, R. Limor, and D.Fliss,  N. Stern.

Institute of Endocrinology, Metabolism and Hypertension and *Institute of Pathology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, ISRAEL.

Background: Estrogen receptors (ER), vitamin D receptors (VDR) and 1a- hydroxylase 25- hydroxyvitamin D (1OHase) mRNA are expressed in various non-reproductive cancer cells types, where they apparently modulate proliferative activity.

Aims: To explore the possibility that human papillary thyroid carcinoma (PTC) are more sensitive to estrogenic effects and/or vitamin D than normal thyroid cells.

Methods: We harvested and cultured papillary thyroid carcinoma (PTC) and adjacent normal thyroid cells obtained during total thyroidectomy from 8 patients.  Gene mRNA expression of ERa, ERb, VDR and 1OHase mRNA was assessed by real time PCR and proliferative response was estimated by 3[H] thymidine incorporation.

Results: Both normal thyroid and PTC cells expressed ERa, ERb, VDR and 1OHase mRNA. Normal thyroid cells had higher abundance than PTC cells of ERa (0.031+0.014 vs. 0.023+0.002 aribitrary units; [AU]; p<0.05) and 1OHase (0.013+0.007 vs. 0.008+0.0005 AU; p<0.05). ERb expression was similar in both cell types. VDR mRNA was very strongly expressed in both cell types but more abundant in the cancer cells than in normal thyroid cells (0.339+0.039 vs. 0.271+.03 AU, respectively; p<0.05). Both normal thyroid and PTC cells showed increase in DNA synthesis in response to estradiol (E2), the ERa selective agonist PPT and the ERb selective agonist DPN, but the proliferative response (relative to untreated cells) was more prominent in cultured PTC than in normal thyroid cells (220  % vs. 135 %, 230% vs. 150%, 190% vs. 130%, respectively;  p<0.01 for all). The modified ERb ligand developed by us from daidzain, cDtboc, inhibited cell growth more effectively in PTC than in normal cells (down to 62, 48, 40% vs. 110, 75 and 65% respectively; p<0.05-0.01). Two different vitamin D non-calcemic analogs [CB, EB] inhibited cell proliferation by 30 and 48%, respectively, and these effects were not further modified by coincubation with cDtboc.

Conclusions: These results are consistent with the hypothesis that endogenous estrogens and vitamin D may affect thyroid cancer cell growth via opposing pathways: cell growth acceleration via induction of ER expression, in association with the induction of VDR and 1OHase to promote the synthesis of 1,25 which is known to inhibit cell proliferation via binding to its receptors.

Nothing to Disclose: AA, DS, EI, OS, EK, FK, RL, DF, NS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm