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

Kazuo Asanoma, Hidenori Kato, Takafumi Inoue, Takao Matsuda, Norio Wake

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)617-626
Number of pages10
JournalJournal of Reproductive Medicine for the Obstetrician and Gynecologist
Volume49
Issue number8
Publication statusPublished - Aug 2004

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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