TY - JOUR
T1 - Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs
AU - van Schaik, R H
AU - Wierikx, C D
AU - Looijenga, L H
AU - Oosterhuis, J W
AU - de Jong, F H
N1 - Funding Information:
The authors wish to thank Dr P ten Dijke for the ActRIA and ActRIB cDNA clones, Dr C de Vries for human placenta RNA, Dr JG Wesseling for the rat ActRIIB clone and Dr G Hotten for the activin PC forward primer. Excellent technical assistance from AJM Gillis and RJLM van Gurp is gratefully acknowledged. This study was sponsored by the Dutch Cancer Society, grant IKMN 92-75.
PY - 1997
Y1 - 1997
N2 - Germ cell development is influenced by activin and inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mouse embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the expression of inhibin/activin subunits, of activin receptors and of the activin-binding protein follistatin was studied in testicular germ cell tumours, using RNAase protection assays. Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed activin type I and type II receptors (ActRI and ActRII respectively). Seminomas expressed significantly lower levels of ActRIIA (P<0.05, Mann-Whitney U-test) and higher levels of ActRIA (P<0.05) and ActRIB (P<0.05) compared with non-seminomas. All tumours expressed inhibin beta-subunit transcripts, which are a prerequisite for activin synthesis. Non-seminomas contained significantly higher levels of the inhibin betaA subunit (P<0.001) compared with seminomas. No activin betaC subunit transcripts could be demonstrated by RNAase protection. Inhibin alpha-subunit expression was absent in the spermatocytic seminomas, in six out of nine seminomas and in 10 out of 11 non-seminomas. Follistatin was expressed predominantly in non-seminomas and spermatocytic seminomas. This expression of activin type I and type II receptors in combination with expression of inhibin beta-subunits indicates that activin may act as a para- or autocrine factor in the regulation of growth and differentiation of tumours of human germ cells.
AB - Germ cell development is influenced by activin and inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mouse embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the expression of inhibin/activin subunits, of activin receptors and of the activin-binding protein follistatin was studied in testicular germ cell tumours, using RNAase protection assays. Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed activin type I and type II receptors (ActRI and ActRII respectively). Seminomas expressed significantly lower levels of ActRIIA (P<0.05, Mann-Whitney U-test) and higher levels of ActRIA (P<0.05) and ActRIB (P<0.05) compared with non-seminomas. All tumours expressed inhibin beta-subunit transcripts, which are a prerequisite for activin synthesis. Non-seminomas contained significantly higher levels of the inhibin betaA subunit (P<0.001) compared with seminomas. No activin betaC subunit transcripts could be demonstrated by RNAase protection. Inhibin alpha-subunit expression was absent in the spermatocytic seminomas, in six out of nine seminomas and in 10 out of 11 non-seminomas. Follistatin was expressed predominantly in non-seminomas and spermatocytic seminomas. This expression of activin type I and type II receptors in combination with expression of inhibin beta-subunits indicates that activin may act as a para- or autocrine factor in the regulation of growth and differentiation of tumours of human germ cells.
KW - Activin Receptors
KW - Activin Receptors, Type I
KW - Follistatin
KW - Germinoma/metabolism
KW - Glycoproteins/metabolism
KW - Growth Substances/metabolism
KW - Humans
KW - Inhibins
KW - Male
KW - Peptides/metabolism
KW - Polymerase Chain Reaction
KW - Prostatic Secretory Proteins
KW - RNA, Messenger/analysis
KW - Receptors, Growth Factor/metabolism
KW - Regression Analysis
KW - Testicular Neoplasms/metabolism
UR - http://www.scopus.com/inward/record.url?scp=0030880537&partnerID=8YFLogxK
U2 - 10.1038/bjc.1997.532
DO - 10.1038/bjc.1997.532
M3 - Article
C2 - 9365168
SN - 0007-0920
VL - 76
SP - 1191
EP - 1198
JO - British journal of cancer
JF - British journal of cancer
IS - 9
ER -