17β-Estradiol Modulates Laryngeal Carcinoma Growth Through Variably-Expressed Membrane-Associated ERs
Objectives: 17β-Estradiol (E2) enhances the growth of certain laryngeal carcinoma cell lines. Despite this, laryngeal cancer is not recognized as an estrogen-responsive cancer, due in part to variability in estrogen receptor (ER) expression in laryngeal carcinomas (LC). This study examined the expression of membrane-associated ERα36 and canonical ERα66 in primary LC and LC cell lines, and to examine the rapid membrane-associated signaling pathways activated by E2 in these cells. Methods: Six LC and matched tumor-surrounding tissue, as well as two LC cell lines (UM-SCC-11A and UM-SCC-12) were analyzed for ERα expression by western blot and RT-PCR. UM-SCC-11A and UM-SCC-12 cell cultures were treated +/- inhibitors, then incubated with E2 for 9min and assessed for proliferation (DNA synthesis), apoptotic markers (total p53 levels and TUNEL staining), and PKC and PLD activity. Results: On average, ERα66 levels were suppressed in primary LCs as compared to cells surrounding the tumor, while ERα36 levels varied among samples. UM-SCC-12 expressed ERα66, but both cell lines expressed ERα36. In UM-SCC-12, E2 stimulated proliferation, reduced apoptosis, and increased PKC and PLD activity. In UM-SCC-11A, E2 decreased proliferation and had no effect on apoptosis. Use of PLD inhibitors, anti-ERα36 antibodies, and b-cyclodextran to destroy caveolae showed that ERα36 does not affect proliferation in either cell line, but inhibiting PLD eliminates E2-mediated proliferation in UM-SCC-12. In UM-SCC-12, caveolae inhibition reduced the effect of E2 on apoptosis, PKC and PLD activity. Antibodies to ERα36 inhibited PKC, but had no effect on PLD activity. Conclusions: These data indicate that LCs are sensitive to E2 and the effect of E2 is mediated by differentreceptors and pathways. These results also suggest that E2-sensitivity may open new treatment avenues for LC patients. The existence of a different E2 receptor should be investigated as a diagnostic and prognostic marker for LC patients.
AADR/CADR Annual Meeting
2018 AADR/CADR Annual Meeting (Fort Lauderdale, Florida) Fort Lauderdale, Florida
2018 0061 Oral Medicine & Pathology Research
Verma, Anjali
( VIRGINIA COMMONWEALTH UNIVERSITY
, RICHMOND
, Virginia
, United States
)
Muktipaty, Chandana
( VIRGINIA COMMONWEALTH UNIVERSITY
, RICHMOND
, Virginia
, United States
)
Schwartz, Nofrat
( Meir Medical Center
, Jerusalem
, Israel
)
Boyan, Barbara
( VIRGINIA COMMONWEALTH UNIVERSITY
, RICHMOND
, Virginia
, United States
; Georgia Institute of Technology
, Atlanta
, Georgia
, United States
)
Schwartz, Zvi
( Virginia Commonwealth University
, Richmond
, Virginia
, United States
; University of Texas Health Science Center at San Antonio
, San Antonio
, Texas
, United States
)
Barbara D. Boyan is an unpaid consultant for Institute Straumann, and a paid consultant for Titan Spine LLC.
Zvi Schwartz is an unpaid consultant for Institute Straumann, and a paid consultant for AB Dental.