Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis

Nakajima,Hideo; Koizumi,Keita; Tanaka,Takuji; Ishigaki,Yasuhito; Yoshitake,Yoshino; Yonekura,Hideto; Sakuma,Tsutomu; Fukushima,Toshihiro; Umehara,Hisanori; Ueno,Soichiro; Minamoto,Toshinari; Motoo,Yoshiharu

doi:10.3892/ijo.2012.1550

Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis

Authors:
- Hideo Nakajima
- Keita Koizumi
- Takuji Tanaka
- Yasuhito Ishigaki
- Yoshino Yoshitake
- Hideto Yonekura
- Tsutomu Sakuma
- Toshihiro Fukushima
- Hisanori Umehara
- Soichiro Ueno
- Toshinari Minamoto
- Yoshiharu Motoo
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Affiliations: Department of Oncology, Ageo Central General Hospital, Ageo, Saitama, Japan, Department of Biophysical Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan, Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan, Department of Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan, Department of Biochemistry, Kanazawa Medical University, Uchinada, Ishikawa, Japan, Department of Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa, Japan, Department of Hematology and Immunology, Kanazawa Medical University, Uchinada, Ishikawa, Japan, Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan, Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, Japan
Published online on: July 10, 2012 https://doi.org/10.3892/ijo.2012.1550
Pages: 1347-1357

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Abstract

Family with sequence similarity 107 (FAM107) proteins consist of two subtypes, FAM107A and FAM107B in mammals, possessing a conserved N-terminal domain of unknown function. Recently we found that FAM107B, an 18 kDa nuclear protein, is expressed in a broad range of tissues and is downregulated in gastrointestinal cancer. Because FAM107B expression is amplified by heat-shock stimulation, we designated it heat shock-inducible tumor small protein (HITS). Although data related to FAM107A as a candidate tumor suppressor have been accumulated, little biological information is available for HITS. In the present study, we examined HITS expression using immunohistochemistry with tissue microarrays and performed detailed statistical analyses. By screening a high-density multiple organ tumor and normal tissue microarray, HITS expression was decreased in tumor tissues of the breast, thyroid, testis and uterine cervix as well as the stomach and colon. Further analysis of tissue microarrays of individual organs showed that loss of HITS expression in cancer tissues was statistically significant and commonly observed in distinct organs in a histological type-specific manner. The HITS expression intensity was inversely correlated with the primary tumor size in breast and thyroid cancers. In addition, effects of tetracycline-inducible HITS expression on tumor growth were investigated in vivo. Forced expression of HITS inhibited tumor xenograft proliferation, compared with the mock-treated tumor xenograft model. These results show that loss of HITS expression is a common phenomenon observed in cancers of distinct organs and involved in tumor development and proliferation.

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