TY - JOUR
T1 - Melanoma-associated antigens in esophageal adenocarcinoma
T2 - Identification of novel MAGE-A10 splice variants
AU - Lin, Jules
AU - Lin, Lin
AU - Thomas, Dafydd G.
AU - Greenson, Joel K.
AU - Giordano, Thomas J.
AU - Robinson, Gregory S.
AU - Barve, Ruteja A.
AU - Weishaar, Frank A.
AU - Taylor, Jeremy M.G.
AU - Orringer, Mark B.
AU - Beer, David G.
PY - 2004/9/1
Y1 - 2004/9/1
N2 - Purpose: The melanoma-associated antigens (MAGEs) are tumor-specific antigens recognized by cytotoxic T lymphocytes. In this study, expression of MAGE family A members was evaluated during the development of esophageal adenocarcinoma (EA) as potential targets for immunotherapy. Experimental Design: MAGE-A mRNA expression was evaluated in 46 samples including Barrett's metaplasia (BM), dysplasia, and EA using oligonucleotide microarrays. Expression of MAGE-A proteins was confirmed by immunohistochemistry on tissue microarrays containing 59 EA, 11 dysplasia, and 9 BM samples and by Western blot. To further evaluate MAGE-A10 expression, reverse transcription-polymerase chain reaction (RT-PCR) products were sequenced, and protein expression was determined using a specific antibody. Results: Overexpression of MAGE-A1, MAGE-A2b, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGE-A10, and MAGE-A12 was found in EAs relative to BM on oligonucleotide microarrays. MAGE-A3 overexpression was confirmed by real-time RT-PCR in 21.4% (6 of 28) of esophageal tumors. Immunohistochemistry on tissue microarray revealed MAGE-A proteins in 20.3% (12 of 59) of EAs and MAGE-A10 staining in 16.9% (10 of 59) of EAs. MAGE-A expression was confirmed by Western blot in several esophageal tumors and in two EA cell lines, Flo-1 and Seg-1, whereas Flo-1 also expressed MAGE-A10. Tumors produced from these cell lines in nude mice retained MAGE-A expression. Interestingly, RT-PCR in primary tumors expressing MAGE-A10 protein revealed additional PCR products that were identified as novel MAGE-A10 alternative splice variants using DNA sequencing. Conclusions: This is the first report of these MAGE-A10 alternative splice sequences, and characterization of MAGE-A expression may provide potential targets for immunotherapy in patients with EA.
AB - Purpose: The melanoma-associated antigens (MAGEs) are tumor-specific antigens recognized by cytotoxic T lymphocytes. In this study, expression of MAGE family A members was evaluated during the development of esophageal adenocarcinoma (EA) as potential targets for immunotherapy. Experimental Design: MAGE-A mRNA expression was evaluated in 46 samples including Barrett's metaplasia (BM), dysplasia, and EA using oligonucleotide microarrays. Expression of MAGE-A proteins was confirmed by immunohistochemistry on tissue microarrays containing 59 EA, 11 dysplasia, and 9 BM samples and by Western blot. To further evaluate MAGE-A10 expression, reverse transcription-polymerase chain reaction (RT-PCR) products were sequenced, and protein expression was determined using a specific antibody. Results: Overexpression of MAGE-A1, MAGE-A2b, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGE-A10, and MAGE-A12 was found in EAs relative to BM on oligonucleotide microarrays. MAGE-A3 overexpression was confirmed by real-time RT-PCR in 21.4% (6 of 28) of esophageal tumors. Immunohistochemistry on tissue microarray revealed MAGE-A proteins in 20.3% (12 of 59) of EAs and MAGE-A10 staining in 16.9% (10 of 59) of EAs. MAGE-A expression was confirmed by Western blot in several esophageal tumors and in two EA cell lines, Flo-1 and Seg-1, whereas Flo-1 also expressed MAGE-A10. Tumors produced from these cell lines in nude mice retained MAGE-A expression. Interestingly, RT-PCR in primary tumors expressing MAGE-A10 protein revealed additional PCR products that were identified as novel MAGE-A10 alternative splice variants using DNA sequencing. Conclusions: This is the first report of these MAGE-A10 alternative splice sequences, and characterization of MAGE-A expression may provide potential targets for immunotherapy in patients with EA.
UR - http://www.scopus.com/inward/record.url?scp=4444319526&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-04-0468
DO - 10.1158/1078-0432.CCR-04-0468
M3 - Article
C2 - 15355897
AN - SCOPUS:4444319526
VL - 10
SP - 5708
EP - 5716
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 17
ER -