HMGB1 and HMGB2 Expression Patterns in Human Papillary Renal Cancers

Takumi Takeuchi, Koichi Sakazume, Akiko Tonooka, Mami Hattori, Masayoshi Zaitsu, Yuta Takeshima, Koji Mikami, Toshimasa Uekusa

Department of Pathology, Kanto Rosai Hospital, Kawasaki, Japan.
Department of Urology, Kanto Rosai Hospital, Kawasaki, Japan.

DOI: 10.4236/oju.2013.31005                

Abstract

High mobility group box (HMGB) proteins are nuclear nonhistone chromosomal proteins that bend DNA, bind preferentially to distorted DNA structures, and promote the assembly of site-specific DNA binding proteins. Recent reports indicate that HMGB1 has a dual function, a cytokine in addition to a nuclear protein. The increased expression of HMGB1 has been reported for several different tumors. Here, we assessed HMGB1 and HMGB2 expressions in two cases of papillary renal cell carcinoma. One case with pT1a, Grade 2 showed HMGB1 expression in the nucleus and cytosol and HMGB2 expression in the nucleus, but not in the cytosol. In the other case, there were three renal tumors, one of which was clear cell renal cell carcinoma with pT1a, Grade 3 and two were papillary renal cell carcinomas, Grade 2 (5 mmand2 mmin the diameter). Both HMGB1 and HMGB2 were expressed in the nucleus and cytosol of papillary carcinoma. In the clear cell carcinoma of this case, HMGB1 expression was stained both in the nucleus and cytosol, while HMGB2 was observed in the nucleus, but not in the cytosol. More samples need to be further investigated in order to draw conclusions concerning HMGB expressions in papillary renal cell carcinomas.

Keywords

Kidney; Papillary; Cancer; HMGB

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. O. Thomas and A. A. Travers, “HMG1 and 2, and Related ‘Architectural’ DNA-Binding Proteins,” Trends in Biochemical Sciences, Vol.26, No. 3, 2001, pp. 167-174. doi:10.1016/S0968-0004(01)01801-1
[2]	S. Muller, L. Ronfani and M. E. Bianchi, “Regulated Expression and Subcellular Localization of HMGB1, a Chromatin Protein with a Cytokine Function,” Journal of Internal Medicine, Vol. 255, No. 3, 2004, pp. 332-343. doi:10.1111/j.1365-2796.2003.01296.x
[3]	A. Jaulmes, S. Thierry, B. Janvier, M. Raymondjean and V. Marechal, “Activation of sPLA2-IIA and PGE2 Production by High Mobility Group Protein B1 in Vascular Smooth Muscle Cells Sensitized by IL-1beta,” The FASEB Journal, Vol. 20, No. 10, 2006, pp.1727-1729. doi:10.1096/fj.05-5514fje
[4]	H. Erlandsson-Harris and U. Andersson, “Mini-Review: The Nuclear Protein HMGB1 as a Proinflammatory Mediator,” European Journal of Immunology, Vol. 34, No. 6, 2004, pp. 1503-1512. doi:10.1002/eji.200424916
[5]	A. Kusume, T. Sasahira, Y. Luo, M. Isobe, N. Nakagawa, N. Tatsumoto, K. Fujii, H. Ohmori and H. Kuniyasu, “Suppression of Dendritic Cells by HMGB1 Is Associated with Lymph Node Metastasis of Human Colon Cancer,” Pathobiology, Vol. 76, No. 4, 2009, pp. 155-162. doi:10.1159/000218331
[6]	M. L. Brezniceanu, K. Volp, S. Bosser, C. Solbach, P. Lichter, S. Joos and M. Zornig, “HMGB1 Inhibits Cell Death in Yeast and Mammalian Cells and Is Abundantly Expressed in Human Breast Carcinoma,” The FASEB Journal, Vol. 17, No. 10, 2003, pp. 1295-1297.
[7]	I. Poser, M. Golob, R. Buettner and A. K. Bosserhoff, “Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype,” Molecular and Cellular Biology, Vol. 23, No. 8, 2003, pp. 2991-2998. doi:10.1128/MCB.23.8.2991-2998.2003
[8]	H. Kuniyasu, Y. Chihara, H. Kondo, H. Ohmori and R. Ukai, “Amphoterin Induction in Prostatic Stromal Cells by Androgen Deprivation Is Associated with Metastatic Prostate Cancer,” Oncology Reports, Vol. 10, No. 6, 2003, pp. 1863-1868.
[9]	M. Gnanasekar, S. Thirugnanam and K. Ramaswamy, “Short Hairpin RNA (shRNA) Constructs Targeting High Mobility Group Box-1 (HMGB1) Expression Leads to Inhibition of Prostate Cancer Cell Survival and Apoptosis,” International Journal of Oncology, Vol. 34, No. 2, 2009, pp. 425-431.
[10]	Y. R. Choi, H. Kim, H. J. Kang, N. G. Kim, J. J. Kim, K. S. Park, Y. K. Paik, H. O. Kim and H. Kim, “Overexpression of High Mobility Group Box 1 in Gastrointestinal Stromal Tumors with KIT Mutation,” Cancer Res, Vol. 63, No. 9, 2003, pp. 2188-2193.
[11]	N. Kostova, S. Zlateva, I. Ugrinova and E. Pasheva, “The Expression of HMGB1 Protein and Its Receptor RAGE in Human Malignant Tumors,” Molecular and Cellular Biology, Vol. 337, No. 1-2, 2010, pp. 251-258. doi:10.1007/s11010-009-0305-0
[12]	J. E. Ellerman, C. K. Brown, M. de Vera, H. J. Zeh, T. Billiar, A. Rubartelli and M. T. Lotze, “Masquerader: High Mobility Group Box-1 and Cancer,” Clinical Cancer Research, Vol.13, No. 10, 2007, pp. 2836-2848. doi:10.1158/1078-0432.CCR-06-1953
[13]	M. Stros, T. Ozaki, A. Bacikova, H. Kageyama and A. Nakagawara, “HMGB1 and HMGB2 Cell-Specifically Down-Regulate the p53- and p73-Dependent Sequence-Specific Transactivation from the Human Bax Gene Promoter,” Journal of Biological Chemistry, Vol. 277, No. 9, 2002, pp. 7157-7164. doi:10.1074/jbc.M110233200
[14]	N. F. Krynetskaia, M. S. Phadke, S. H. Jadhav and E. Y. Krynetskiy, “Chromatin-Associated Proteins HMGB1/2 and PDIA3 Trigger Cellular Response to Chemotherapy-Induced DNA Damage,” Molecular Cancer Therapeutics, Vol. 8, No. 4, 2009, pp. 864-872. doi:10.1158/1535-7163.MCT-08-0695
[15]	T. Takeuchi, K. Sakazume, A. Tonooka, M. Zaitsu, Y. Takeshima, K. Mikami and T. Uekusa, “Cytosolic HM-GB1 Expression in Human Renal Clear Cell Cancer Indicates Higher Pathological T Classifications and Tumor Grades,” Urology Journal. (In Press)
[16]	W. M. Linehan, R. Srinivasan and L. S. Schmidt, “The Genetic Basis of Kidney Cancer: A Metabolic Disease,” Nature Reviews Urology, Vol. 7, No. 5, 2010, pp. 277-285. doi:10.1038/nrurol.2010.47
[17]	S. Steffens, M. Janssen, F. C. Roos, F. Becker, S. Schumacher, C. Seidel, G. Wegener, J. W. Thuroff, R. Hofmann, M. St?ckle, S. Siemer, M. Schrader, A. Hartmann, M. A. Kuczyk, K. Junker and A. J. Schrader, “Incidence and Long-Term Prognosis of Papillary Compared to Clear Cell Renal Cell Carcinoma—A Multicentre Study,” European Journal of Cancer, Vol. 48, No. 15, 2012, pp. 2347-2352. doi:10.1016/j.ejca.2012.05.002
[18]	M. Waldert, A. Haitel, M. Marberger, D. Katzenbeisser, M. Ozsoy, E. Stadler and M. Remzi, “Comparison of Type I and II Papillary Renal Cell Carcinoma (RCC) and Clear Cell RCC,” BJU International, Vol. 102, No. 10, 2008, pp. 1381-1384.