Oncogenic HMGA2: short or small?

  1. Andrew R.J. Young and
  2. Masashi Narita1
  1. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom

This extract was created in the absence of an abstract.

The High Mobility Group A (HMGA) family of proteins are architectural transcription factors that bind to DNA and introduce structural alterations in chromatin. The HMGA family consists of two members, HMGA1 and HMGA2, which are encoded by separate genes. As one of the major nonhistone chromosomal proteins, HMGA proteins are multifunctional and are involved in many fundamental cellular processes, including gene regulation, cell cycle, differentiation, and viral integration (Reeves 2001). Not surprisingly, therefore, HMGA mutations contribute to many common diseases, including benign and malignant tumors (Sgarra et al. 2004), obesity (Anand and Chada 2000), diabetes (Foti et al. 2005), and atherosclerosis (Schlueter et al. 2005). HMGA proteins are relatively abundant in the early embryo, where cells are proliferating rapidly, whereas they are undetectable in terminally differentiated cells (Sgarra et al. 2004). hmga2-deficient mouse embryonic fibroblasts (MEFs) grow more slowly than wild-type MEFs (Zhou et al. 1995), suggesting that HMGA2 confers a growth advantage. Consistent with this observation, HMGA is indeed oncogenic and is up-regulated in many tumors (see below). However, it was recently shown that HMGA proteins are also involved in cellular senescence, a state of “permanent” cell cycle arrest, adding further diversity to the many facets of the HMGA proteins (Narita et al. 2006).

HMGA proteins are primarily, but not exclusively, up-regulated in tumors of mesenchymal origin. Up-regulation of the HMGA gene products often results from genetic alterations such as gene amplification and translocation. Rearrangement of the HMGA2 gene by reciprocal translocations in particular, is frequently observed in benign tumors such as lipomas, lung hamartomas, uterine leiomyomas, endothelial polyps, fibroadenomas, and adenolipomas of the breast (Ashar et al. 1995; Kazmierczak et al. 1995, 1996; Schoenmakers et al. 1995). HMGA is also involved in malignant tumors such as liposarcomas and osteosarcomas, acute lymphoblastic leukemia, as …

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