Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1

Yehudit Birger, Frédéric Catez, Takashi Furusawa, Jae Hwan Lim, Marta Prymakowska-Bosak, Katherine L. West, Yuri V. Postnikov, Diana C. Haines, Michael Bustin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

We report that loss of HMGN1, a nucleosome-binding protein that alters the compaction of the chromatin fiber, increases the cellular sensitivity to ionizing radiation and the tumor burden of mice. The mortality and tumor burden of ionizing radiation-treated Hmgn1-/- mice is higher than that of their Hmgn1+/+ littermates. Hmgn1-/- fibroblasts have an altered G2-M checkpoint activation and are hypersensitive to ionizing radiation. The ionizing radiation hypersensitivity and the aberrant G 2-M checkpoint activation of Hmgn1-/- fibroblasts can be reverted by transfections with plasmids expressing wild-type HMGN1, but not with plasmids expressing mutant HMGN proteins that do not bind to chromatin. Transformed Hmgn1-/- fibroblasts grow in soft agar and produce tumors in nude mice with a significantly higher efficiency than Hmgn1+/+ fibroblasts, suggesting that loss of HMGN1 protein disrupts cellular events controlling proliferation and growth. Hmgn1-/- mice have a higher incidence of multiple malignant tumors and metastases than their Hmgn1 +/+ littermates. We suggest that HMGN1 optimizes the cellular response to ionizing radiation and to other tumorigenic events; therefore, loss of this protein increases the tumor burden in mice.

Original languageEnglish
Pages (from-to)6711-6718
Number of pages8
JournalCancer Research
Volume65
Issue number15
DOIs
StatePublished - 1 Aug 2005
Externally publishedYes

Funding

FundersFunder number
National Cancer InstituteZ01BC004496

    Fingerprint

    Dive into the research topics of 'Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1'. Together they form a unique fingerprint.

    Cite this