Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells

• Published in: Carcinogenesis (New York) 2002-11, Vol.23 (11), p.1885-1895
• Main Authors: Lottin, Séverine, Adriaenssens, Eric, Dupressoir, Thierry, Berteaux, Nathalie, Montpellier, Claire, Coll, Jean, Dugimont, Thierry, Curgy, Jean Jacques
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Animals; Biological and medical sciences; bovine serum albumin; Breast Neoplasms - genetics; Breast Neoplasms - pathology; BSA; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Disease Progression; Epithelial Cells - pathology; FCS; Female; fetal calf serum; Fundamental and applied biological sciences. Psychology; GAPDH; Gene Expression Regulation, Neoplastic; glyceraldehyde-3′-phosphate dehydrogenase; Humans; MEM; Mice; Mice, SCID; minimal essential medium; Molecular and cellular biology; Neoplasm Transplantation; open reading frames; ORF; paraformaldehyde; PBS; PFA; Phenotype; phosphate buffer saline; Recombinant Fusion Proteins - physiology; RNA, Long Noncoding; RNA, Untranslated - genetics; RNA, Untranslated - physiology; SHE; Syrian hamster embryo; Transfection; Tumor Stem Cell Assay
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/23.11.1885

The maternally expressed H19 gene is transcribed as an untranslated RNA that serves as a riboregulator. We have previously reported that this transcript accumulates in epithelial cells in ~10% of breast cancers. To gain further insight on how the overexpression of the H19 gene affects the phenotype of human breast epithelial cells, we investigated the oncogenic potential of RNA that was abundantly expressed from MDA-MB-231 breast cancer cells stably transfected with the genomic sequence of the human H19 gene. The amount of H19 RNA did not affect cell proliferation capacity, timing of cell cycle phases or anchorage-dependent ability of H19-transfected clones in vitro. But in anchorage-independent growth assays the H19-recombined cells formed more and larger colonies in soft-agar versus control cells. To explore this phenotypic change, we analysed tumour development after subcutaneous injection of H19-recombined cells into scid mice. Results showed that H19 overexpression promotes tumour progression. These data support the hypothesis that an overload of H19 transcript is associated with cells exhibiting higher tumorigenic phenotypes and therefore we conclude that the H19 gene has oncogenic properties in breast epithelial cells.