HMGA1 protein expression sensitizes cells to cisplatin-induced cell death

Gustavo Baldassarre, Barbara Belletti, Sabrina Battista, Milena S. Nicoloso, Francesca Pentimalli, Monica Fedele, Carlo M. Croce, Alfredo Fusco

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins. Although their expression is very low or absent in many adult tissues, HMGA1 proteins have been frequently found to be upregulated in human cancers and are expressed at high levels during embryogenesis, suggesting they could have a role in highly proliferating cells. We have previously demonstrated that HMGA1 expression in primary breast cancer and mammary carcinoma derived cell lines inversely correlated with BRCA1 expression and that HMGA1 is able to downregulate the expression of BRCA1 gene by binding directly to its promoter region. Being BRCA1 protein expression strictly linked to the DNA repair activity of the cell, we investigated whether HMGA1 expression was able to influence cellular responses to DNA damage. Here, we report that high expression levels of HMGA1 proteins in MCF-7 or mouse embryonic stem cells results in diminished BRCA1 expression and enhanced sensitivity to Cisplatin and Bleomycin. The increased DNA damage-induced cell death in HMGA1-expressing cells is likely due to a diminished cellular DNA repair activity. Therefore, we propose that high expression of HMGA1 protein in human malignant neoplasias, acting on BRCA1 expression, could contribute to the progression of malignant transformation influencing the response of the cells to the damaged DNA.

Original languageEnglish
Pages (from-to)6809-6819
Number of pages11
JournalOncogene
Volume24
Issue number45
DOIs
Publication statusPublished - Oct 13 2005

Fingerprint

Cisplatin
Cell Death
Breast Neoplasms
Proteins
DNA Repair
DNA Damage
BRCA1 Protein
AT Rich Sequence
BRCA1 Gene
DNA
Bleomycin
Genetic Promoter Regions
Chromatin
Embryonic Development
Neoplasms
Transcription Factors
Down-Regulation
Cell Line
Genes

Keywords

  • Apoptosis
  • BRCA1
  • DNA damage
  • ES cells
  • HMGA1
  • Knockout

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Baldassarre, G., Belletti, B., Battista, S., Nicoloso, M. S., Pentimalli, F., Fedele, M., ... Fusco, A. (2005). HMGA1 protein expression sensitizes cells to cisplatin-induced cell death. Oncogene, 24(45), 6809-6819. https://doi.org/10.1038/sj.onc.1208831

HMGA1 protein expression sensitizes cells to cisplatin-induced cell death. / Baldassarre, Gustavo; Belletti, Barbara; Battista, Sabrina; Nicoloso, Milena S.; Pentimalli, Francesca; Fedele, Monica; Croce, Carlo M.; Fusco, Alfredo.

In: Oncogene, Vol. 24, No. 45, 13.10.2005, p. 6809-6819.

Research output: Contribution to journalArticle

Baldassarre, G, Belletti, B, Battista, S, Nicoloso, MS, Pentimalli, F, Fedele, M, Croce, CM & Fusco, A 2005, 'HMGA1 protein expression sensitizes cells to cisplatin-induced cell death', Oncogene, vol. 24, no. 45, pp. 6809-6819. https://doi.org/10.1038/sj.onc.1208831
Baldassarre, Gustavo ; Belletti, Barbara ; Battista, Sabrina ; Nicoloso, Milena S. ; Pentimalli, Francesca ; Fedele, Monica ; Croce, Carlo M. ; Fusco, Alfredo. / HMGA1 protein expression sensitizes cells to cisplatin-induced cell death. In: Oncogene. 2005 ; Vol. 24, No. 45. pp. 6809-6819.
@article{31b5037552e14b7ca3eedbbde84b66c8,
title = "HMGA1 protein expression sensitizes cells to cisplatin-induced cell death",
abstract = "HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins. Although their expression is very low or absent in many adult tissues, HMGA1 proteins have been frequently found to be upregulated in human cancers and are expressed at high levels during embryogenesis, suggesting they could have a role in highly proliferating cells. We have previously demonstrated that HMGA1 expression in primary breast cancer and mammary carcinoma derived cell lines inversely correlated with BRCA1 expression and that HMGA1 is able to downregulate the expression of BRCA1 gene by binding directly to its promoter region. Being BRCA1 protein expression strictly linked to the DNA repair activity of the cell, we investigated whether HMGA1 expression was able to influence cellular responses to DNA damage. Here, we report that high expression levels of HMGA1 proteins in MCF-7 or mouse embryonic stem cells results in diminished BRCA1 expression and enhanced sensitivity to Cisplatin and Bleomycin. The increased DNA damage-induced cell death in HMGA1-expressing cells is likely due to a diminished cellular DNA repair activity. Therefore, we propose that high expression of HMGA1 protein in human malignant neoplasias, acting on BRCA1 expression, could contribute to the progression of malignant transformation influencing the response of the cells to the damaged DNA.",
keywords = "Apoptosis, BRCA1, DNA damage, ES cells, HMGA1, Knockout",
author = "Gustavo Baldassarre and Barbara Belletti and Sabrina Battista and Nicoloso, {Milena S.} and Francesca Pentimalli and Monica Fedele and Croce, {Carlo M.} and Alfredo Fusco",
year = "2005",
month = "10",
day = "13",
doi = "10.1038/sj.onc.1208831",
language = "English",
volume = "24",
pages = "6809--6819",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "45",

}

TY - JOUR

T1 - HMGA1 protein expression sensitizes cells to cisplatin-induced cell death

AU - Baldassarre, Gustavo

AU - Belletti, Barbara

AU - Battista, Sabrina

AU - Nicoloso, Milena S.

AU - Pentimalli, Francesca

AU - Fedele, Monica

AU - Croce, Carlo M.

AU - Fusco, Alfredo

PY - 2005/10/13

Y1 - 2005/10/13

N2 - HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins. Although their expression is very low or absent in many adult tissues, HMGA1 proteins have been frequently found to be upregulated in human cancers and are expressed at high levels during embryogenesis, suggesting they could have a role in highly proliferating cells. We have previously demonstrated that HMGA1 expression in primary breast cancer and mammary carcinoma derived cell lines inversely correlated with BRCA1 expression and that HMGA1 is able to downregulate the expression of BRCA1 gene by binding directly to its promoter region. Being BRCA1 protein expression strictly linked to the DNA repair activity of the cell, we investigated whether HMGA1 expression was able to influence cellular responses to DNA damage. Here, we report that high expression levels of HMGA1 proteins in MCF-7 or mouse embryonic stem cells results in diminished BRCA1 expression and enhanced sensitivity to Cisplatin and Bleomycin. The increased DNA damage-induced cell death in HMGA1-expressing cells is likely due to a diminished cellular DNA repair activity. Therefore, we propose that high expression of HMGA1 protein in human malignant neoplasias, acting on BRCA1 expression, could contribute to the progression of malignant transformation influencing the response of the cells to the damaged DNA.

AB - HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins. Although their expression is very low or absent in many adult tissues, HMGA1 proteins have been frequently found to be upregulated in human cancers and are expressed at high levels during embryogenesis, suggesting they could have a role in highly proliferating cells. We have previously demonstrated that HMGA1 expression in primary breast cancer and mammary carcinoma derived cell lines inversely correlated with BRCA1 expression and that HMGA1 is able to downregulate the expression of BRCA1 gene by binding directly to its promoter region. Being BRCA1 protein expression strictly linked to the DNA repair activity of the cell, we investigated whether HMGA1 expression was able to influence cellular responses to DNA damage. Here, we report that high expression levels of HMGA1 proteins in MCF-7 or mouse embryonic stem cells results in diminished BRCA1 expression and enhanced sensitivity to Cisplatin and Bleomycin. The increased DNA damage-induced cell death in HMGA1-expressing cells is likely due to a diminished cellular DNA repair activity. Therefore, we propose that high expression of HMGA1 protein in human malignant neoplasias, acting on BRCA1 expression, could contribute to the progression of malignant transformation influencing the response of the cells to the damaged DNA.

KW - Apoptosis

KW - BRCA1

KW - DNA damage

KW - ES cells

KW - HMGA1

KW - Knockout

UR - http://www.scopus.com/inward/record.url?scp=22144474858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22144474858&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1208831

DO - 10.1038/sj.onc.1208831

M3 - Article

C2 - 16007157

AN - SCOPUS:22144474858

VL - 24

SP - 6809

EP - 6819

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 45

ER -