The testis-specific expression pattern of the growth hormone/placental lactogen (GH/PL) gene cluster changes with malignancy

Growth hormone (GH) and placental lactogen (PL) gene transcription patterns in testicular germ cell tumors (GCT) and normal testicular tissue were com paratively investigated to identify GH/PL gene products associated with the development of GCT. This tvas done by nondiscriminative reverse transcript ase-polymerase chain reaction (RT-PCR), amplifying all major transcripts of any of the 5 GH/PL genes-GH-N(ormal), GH-V(ariant), PL-A, PC-B, PG-L(ike)- and subsequent analytical restriction enzyme analyses of 5'-end radioactive ly labeled cDNA. Surprisingly, all nonseminomatous GCT (NSGCT; n = 9) expre ssed GH-N, PL-A/B, and PL-L transcripts (9 of 9). Seminoma (n = 7) showed a distinctly unique pattern of GH-N and PL-A/B. GH-V products, which are hal lmarks of the normal healthy testis, were not detected in any testicular ca ncer specimen (0 of 16). The fact that both seminomatous and NSGCT showed a lterations in the same gene cluster indicates a pathogenetic relationship. Two choriocarcinoma cell lines of conceptus origin, BeWo and JAR, clearly d iffering from the male counterparts, exhibited a placental-derived pattern of PL-A/B and GH-V. Obviously, profound differences exist between conceptus and male germ cell GH/PL gene cluster transcription. In summary, the uniqu e testicular pattern of GH/PL gene expression changes significantly and in directed ways with malignancy. Loss of GH-V gene expression in testicular G CT compared with normal testis and loss (seminoma) or mutation (NSGCT) of P L-L gene products might have significance in terms of the relationship betw een these tumors and for testicular GCT development. Copyright (C) 1999 by W.B. Saunders Company.