Tumoral FOXP3 has potential oncogenic function in conjunction with the p53 tumor suppressor protein and infiltrated Tregs in human breast carcinomas

Pathology Research and Practice

Volumn 209, Issue 12, 2013, Pages 767-773

  Won, Kyu Yeoun ^a   Kim, Hyun Soo ^b   Sung, Ji Youn ^a   Kim, Gou Young ^a   Lee, Juhie ^a   Park, Yong Koo ^a   Kim, Youn Wha ^a   Suh, Jung Ho ^b   Lim, Sung Jig ^a  

^a Kyung Hee University College of Medicine   (South Korea)

^b Kyung Hee University Hospital   (South Korea)

Author keywords

Breast carcinoma; FOXP3; P53; Treg

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; KI 67 ANTIGEN; PROTEIN P53; TRANSCRIPTION FACTOR FOXP3;

ADULT; AGED; ARTICLE; BREAST CARCINOMA; CANCER GRADING; CANCER SURVIVAL; CLINICAL FEATURE; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE FREE SURVIVAL; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; MOLECULAR PATHOLOGY; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; UPREGULATION;

BREAST CARCINOMA; FOXP3; P53; TREG;

ADULT; AGED; AGED, 80 AND OVER; BREAST NEOPLASMS; CARCINOMA; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; MIDDLE AGED; PROGNOSIS; T-LYMPHOCYTES, REGULATORY; TUMOR MARKERS, BIOLOGICAL; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84887818302     PISSN: 03440338     EISSN: 16180631     Source Type: Journal    
DOI: 10.1016/j.prp.2013.08.010     Document Type: Article

References (26)

1. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299:1057-1061.
2. Ziegler S.F. FOXP3: of mice and men. Annu. Rev. Immunol. 2006, 24:209-226.
3. Bennett C.L., Yoshioka R., Kiyosawa H., Barker D.F., Fain P.R., Shigeoka A.O., Chance P.F. X-Linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23-Xq13.3. Am. J. Hum. Genet. 2000, 66:461-468.
4. Curiel T.J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., Evdemon-Hogan M., Conejo-Garcia J.R., Zhang L., Burow M., Zhu Y., Wei S., Kryczek I., Daniel B., Gordon A., Myers L., Lackner A., Disis M.L., Knutson K.L., Chen L., Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 2004, 10:942-949.
5. Bates G.J., Fox S.B., Han C., Leek R.D., Garcia J.F., Harris A.L., Banham A.H. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J. Clin. Oncol. 2006, 24:5373-5380.
6. Hinz S., Pagerols-Raluy L., Oberg H.H., Ammerpohl O., Grussel S., Sipos B., Grutzmann R., Pilarsky C., Ungefroren H., Saeger H.D., Kloppel G., Kabelitz D., Kalthoff H. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res. 2007, 67:8344-8350.
7. Jung D.J., Jin D.H., Hong S.W., Kim J.E., Shin J.S., Kim D., Cho B.J., Hwang Y.I., Kang J.S., Lee W.J. Foxp3 expression in p53-dependent DNA damage responses. J. Biol. Chem. 2010, 285:7995-8002.
8. Ebert L.M., Tan B.S., Browning J., Svobodova S., Russell S.E., Kirkpatrick N., Gedye C., Moss D., Ng S.P., MacGregor D., Davis I.D., Cebon J., Chen W. The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res. 2008, 68:3001-3009.
9. Merlo A., Casalini P., Carcangiu M.L., Malventano C., Triulzi T., Menard S., Tagliabue E., Balsari A. FOXP3 expression and overall survival in breast cancer. J. Clin. Oncol. 2009, 27:1746-1752.
10. Tao H., Mimura Y., Aoe K., Kobayashi S., Yamamoto H., Matsuda E., Okabe K., Matsumoto T., Sugi K., Ueoka H. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer 2012, 75:95-101.
11. Bohling S.D., Allison K.H. Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod. Pathol. 2008, 21:1527-1532.
12. Wolff A.C., Hammond M.E., Schwartz J.N., Hagerty K.L., Allred D.C., Cote R.J., Dowsett M., Fitzgibbons P.L., Hanna W.M., Langer A., McShane L.M., Paik S., Pegram M.D., Perez E.A., Press M.F., Rhodes A., Sturgeon C., Taube S.E., Tubbs R., Vance G.H., van de Vijver M., Wheeler T.M., Hayes D.F. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J. Clin. Oncol. 2007, 25:118-145.
13. Ito T., Hanabuchi S., Wang Y.H., Park W.R., Arima K., Bover L., Qin F.X., Gilliet M., Liu Y.J. Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 2008, 28:870-880.
14. Fontenot J.D., Rasmussen J.P., Williams L.M., Dooley J.L., Farr A.G., Rudensky A.Y., Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005, 22:329-341.
15. Zuo T., Liu R., Zhang H., Chang X., Liu Y., Wang L., Zheng P. FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J. Clin. Invest. 2007, 117:3765-3773.
16. Wang L., Liu R., Li W., Chen C., Katoh H., Chen G.Y., McNally B., Lin L., Zhou P., Zuo T., Cooney K.A., Liu Y., Zheng P. Somatic single hits inactivate the X-linked tumor suppressor FOXP3 in the prostate. Cancer Cell 2009, 16:336-346.
17. Yoshii M., Tanaka H., Ohira M., Muguruma K., Iwauchi T., Lee T., Sakurai K., Kubo N., Yashiro M., Sawada T., Hirakawa K. Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach. Br. J. Cancer 2012, 106:1668-1674.
18. Wang W.H., Jiang C.L., Yan W., Zhang Y.H., Yang J.T., Zhang C., Yan B., Zhang W., Han W., Wang J.Z., Zhang Y.Q. FOXP3 expression and clinical characteristics of hepatocellular carcinoma. World J. Gastroenterol. 2010, 16:5502-5509.
19. Harris S.L., Levine A.J. The p53 pathway: positive and negative feedback loops. Oncogene 2005, 24:2899-2908.
20. Zuo T., Wang L., Morrison C., Chang X., Zhang H., Li W., Liu Y., Wang Y., Liu X., Chan M.W., Liu J.Q., Love R., Liu C.G., Godfrey V., Shen R., Huang T.H., Yang T., Park B.K., Wang C.Y., Zheng P. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell 2007, 129:1275-1286.
21. Mizukami Y., Kono K., Kawaguchi Y., Akaike H., Kamimura K., Sugai H., Fujii H. Localisation pattern of Foxp3+ regulatory T cells is associated with clinical behaviour in gastric cancer. Br. J. Cancer 2008, 98:148-153.
22. Gao Q., Qiu S.J., Fan J., Zhou J., Wang X.Y., Xiao Y.S., Xu Y., Li Y.W., Tang Z.Y. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol. 2007, 25:2586-2593.
23. Petersen R.P., Campa M.J., Sperlazza J., Conlon D., Joshi M.B., Harpole D.H., Patz E.F. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 2006, 107:2866-2872.
24. Shimizu K., Nakata M., Hirami Y., Yukawa T., Maeda A., Tanemoto K. Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J. Thorac. Oncol. 2010, 5:585-590.
25. Hiraoka N., Onozato K., Kosuge T., Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res. 2006, 12:5423-5434.
26. Nair S., Boczkowski D., Fassnacht M., Pisetsky D., Gilboa E. Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res. 2007, 67:371-380.