Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells

M. Fedele, G. M. Pierantoni, M. T. Berlingieri, S. Battista, G. Baldassarre, N. Munshi, M. Dentice, D. Thanos, M. Santoro, G. Viglietto, A. Fusco

Research output: Contribution to journalArticle

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Abstract

The high mobility group (HMG) proteins (HMGA1a, HMGA1b, and HMGA2) bind to DNA and interact with various transcriptional factors. Therefore, they play an important role in chromatin organization. HMGA protein expression is low in normal adult tissues, but abundant during embryonic development and in several experimental and human tumors. Blockage of HMGA expression inhibits the transformation of rat thyroid PC CI 3 cells treated with oncogene-carrying retroviruses, thus implicating HMGA in rat thyroid transformation. To better understand the role of HMGA and to establish whether its up-regulated expression is sufficient to induce the transformed phenotype, we generated PC CI 3 cells that overexpress the protein. We demonstrate that HMGA1b protein overexpression does not transform normal rat thyroid PC CI 3 cells, but it deregulates their cell cycle: cells enter S-phase earlier and the G2-M transition is delayed. HMGA1-overexpressing cells undergo apoptosis through a pathway involving caspase-3 activation, probably consequent to the conflict between mitogenic pressure and the inability to proceed through the cell cycle. Using various HMGA1b gene mutations, we found that the third AT-hook domain and the acetylation site K60 are the protein regions required for induction of apoptosis in PC CI 3 cells. In conclusion, although HMGA1 protein overexpression is associated with the malignant phenotype of rat and human thyroid cells, it does not transform normal thyroid cells in culture but leads them to programmed cell death.

Original languageEnglish
Pages (from-to)4583-4590
Number of pages8
JournalCancer Research
Volume61
Issue number11
Publication statusPublished - Jun 1 2001

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HMGA Proteins
Cell Cycle
Thyroid Gland
Apoptosis
Proteins
HMGA1b Protein
AT-Hook Motifs
High Mobility Group Proteins
Phenotype
Retroviridae
Acetylation
S Phase
Oncogenes
Caspase 3
Chromatin
Embryonic Development
Cell Death
Cell Culture Techniques
Pressure
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fedele, M., Pierantoni, G. M., Berlingieri, M. T., Battista, S., Baldassarre, G., Munshi, N., ... Fusco, A. (2001). Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells. Cancer Research, 61(11), 4583-4590.

Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells. / Fedele, M.; Pierantoni, G. M.; Berlingieri, M. T.; Battista, S.; Baldassarre, G.; Munshi, N.; Dentice, M.; Thanos, D.; Santoro, M.; Viglietto, G.; Fusco, A.

In: Cancer Research, Vol. 61, No. 11, 01.06.2001, p. 4583-4590.

Research output: Contribution to journalArticle

Fedele, M, Pierantoni, GM, Berlingieri, MT, Battista, S, Baldassarre, G, Munshi, N, Dentice, M, Thanos, D, Santoro, M, Viglietto, G & Fusco, A 2001, 'Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells', Cancer Research, vol. 61, no. 11, pp. 4583-4590.
Fedele M, Pierantoni GM, Berlingieri MT, Battista S, Baldassarre G, Munshi N et al. Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells. Cancer Research. 2001 Jun 1;61(11):4583-4590.
Fedele, M. ; Pierantoni, G. M. ; Berlingieri, M. T. ; Battista, S. ; Baldassarre, G. ; Munshi, N. ; Dentice, M. ; Thanos, D. ; Santoro, M. ; Viglietto, G. ; Fusco, A. / Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells. In: Cancer Research. 2001 ; Vol. 61, No. 11. pp. 4583-4590.
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