Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma.
BACKGROUND
The seminoma class of testicular germ cell tumor (TGCT) are characterized by a morphological resemblance to primordial germ cells (PGCs) or gonocytes, and chromosome duplications at 12p. Recently, it was determined that human embryonic stem cells (hESCs) express genes in common with PGCs, and that three of these genes, GDF3, STELLAR, and NANOG, are located on 12p. The current study was designed to identify whether expression of these 12p genes were elevated in seminoma relative to normal testis, and to determine whether elevated expression was unique to seminoma.


METHODS
Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to assess gene expression in seminoma samples relative to normal testis and endpoint PCR was used to identify the presence or absence of these genes in breast carcinoma.


RESULTS
GDF3 expression was increased in eight of nine seminomas compared with normal testis, whereas NANOG, OCT4, or both were expressed at the highest levels in seminoma compared with all other markers analyzed. In addition, the NANOG protein was expressed in the majority of seminoma cells. The adult meiotic germ cell markers BOULE and TEKT1 were undetectable in seminoma, whereas the embryonic and adult germ cell markers DAZL and VASA were significantly reduced. Analysis of these markers in breast carcinoma and the MCF7 breast carcinoma cell line revealed that a core hESC-transcriptional profile could be identified consisting of OCT4, NANOG, STELLAR, and GDF3 and that NANOG protein could be detected in breast carcinoma.


CONCLUSIONS
These observations suggest that seminoma and breast carcinoma express a common stem cell profile and that the expression of DAZL and VASA in seminoma mark the germ cell origin of seminoma that is absent in breast carcinoma. Our findings suggest that stem cell genes may either play a direct role in different types of carcinoma progression or serve as valuable markers of tumorigenesis.
Ezeh
Uche I
UI
Program in Human Embryonic Stem Cell Biology, Center for Reproductive Sciences, Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, California 94143-0556, USA.
Turek
Paul J
PJ
Reijo
Renee A
RA
Clark
Amander T
AT
D015153:Blotting, Western; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008954:Models, Biological; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C466105:DPPA3 protein, human; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011506:Proteins