Analysis of a candidate gene associated with growth suppression of choriocarcinoma and differentiation of trophoblasts.

OBJECTIVE

To isolate a choriocarcinoma suppressor gene and analyze its structure and function.

STUDY DESIGN

We constructed a polymerase chain reaction-based subtracted fragmentary cDNA library between normal placental villi and choriocarcinoma cell line CC1. A novel homeobox gene, designated NECC1 (not expressed in differ choriocarcinoma clone 1), is included in this library. We analyzed the structure and function of NECC1 with molecular biology.

RESULTS

NECC1 comprises an open reading frame of 219 nucleotides encoding 73 amino acids and contains a homeodomain as a consensus motif. NECC1 is located on human chromosome 4q11-q12, and its expression is ubiquitous in the brain, placenta, lung, smooth muscle, uterus, bladder, kidney and spleen. Normal placental villi abundantly expressed NECC1, but all choriocarcinoma cell lines examined and most surgically removed choriocarcinoma tissue samples failed to express it. We transfected this gene into choriocarcinoma cell lines and observed remarkable alterations in cell morphology and suppression of in vivo tumorigenesis. Induction of chorionic somatomammotropin hormone 1 by NECC1 transfection suggested differentiation of choriocarcinoma cells to syncytiotrophoblast-like cells.

CONCLUSION

Our results suggest that loss of NECC1 expression is involved in malignant conversion of placental trophoblasts.