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Foci formation of P53‐binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis
Author(s) -
Nakashima Masahiro,
Suzuki Keiji,
Meirmanov Serik,
Naruke Yuki,
MatsuuMatsuyama Mutsumi,
Shichijo Kazuko,
Saenko Vladimir,
Kondo Hisayoshi,
Hayashi Tomayoshi,
Ito Masahiro,
Yamashita Shunichi,
Sekine Ichiro
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23223
Subject(s) - carcinogenesis , thyroid , thyroid cancer , genome instability , cancer research , biology , cancer , immunofluorescence , nuclear protein , pathology , dna damage , endocrinology , medicine , dna , transcription factor , antibody , immunology , gene , genetics
Defective DNA damage response (DDR) can result in genomic instability (GIN) and lead to the transformation into cancer. P53‐binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DNA double strand breaks (DSBs) and rapidly form nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker for endogenous DSBs reflecting GIN. Although it has been proposed that GIN has a crucial role in the progression of thyroid neoplasms, the significance of GIN during thyroid tumorigenesis remains unclear, particularly in patients. We analyzed, therefore, the level of GIN, as detected with immunofluorescence of 53BP1, in 40 cases of resected thyroid tissues. This study demonstrated a number of nuclear 53BP1 foci in thyroid cancers, suggesting a constitutive activation of DDR in thyroid cancer cells. Because follicular adenoma also showed a few 53BP1 nuclear foci, GIN might be induced at a precancerous stage of thyroid tumorigenesis. Furthermore, high‐grade thyroid cancers prominently exhibited an intense and heterogeneous nuclear staining of 53BP1 immunoreactivity, which was also observed in radiation‐associated cancers and in mouse colonic crypts as a delayed response to a high dose ionizing radiation, suggesting increased GIN with progression of cancer. Thus, the present study demonstrated a difference in the staining pattern of 53BP1 during thyroid carcinogenesis. We propose that immunofluorescence analysis of 53BP1 expression can be a useful tool to estimate the level of GIN and, simultaneously, the malignant potency of human thyroid tumors. © 2007 Wiley‐Liss, Inc.