MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development.
BACKGROUND
Cancer/testis antigens (CTAs) are expressed in several cancers and during normal adult male germ cell differentiation. Little is known about their role in fetal development of human germ cells.


METHODS
We examined expression of the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads by single and double immunohistochemical staining.


RESULTS
We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ cells and the staining intensity of all three CTAs peaked during the second trimester and gradually decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1 expression terminated around birth, whereas NY-ESO-1 expression persisted through the neonatal stage and GAGE expression was maintained until adulthood. The population of GAGE-expressing male and female germ cells partially overlapped the population of OCT4-positive cells, whereas MAGE-A1 and NY-ESO-1 were clearly expressed only by OCT4-negative cells.


CONCLUSIONS
Our results suggest that MAGE-A1 and NY-ESO-1 are associated with highly proliferating germ cells, whereas GAGE proteins have a more general function in germ cells unrelated to any specific developmental stage. The recognition of differential cellular expression of GAGE, MAGE-A1, NY-ESO-1 and OCT4 may help define biologically distinct germ cell subpopulations.
Gjerstorff
Morten F
MF
Medical Biotechnology Center, Institute of Medical Biology, University of Southern Denmark, Odense C, Denmark.
Kock
Kirsten
K
Nielsen
Ole
O
Ditzel
Henrik J
HJ
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010053:Ovary / Q000196:embryology* / Q000378:metabolism; D013737:Testis / Q000196:embryology*; D014018:Tissue Distribution
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C095365:GAGE1 protein, human; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human