TY - JOUR

T1 - In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3.

AU - Sommer, V H

AU - Clemmensen, O J

AU - Nielsen, O

AU - Wasik, M

AU - Lovato, P

AU - Brender, C

AU - Eriksen, K W

AU - Woetmann, A

AU - Kaestel, C G

AU - Nissen, Mogens Holst

AU - Ropke, C

AU - Skov, S

AU - Ødum, N

N1 - Keywords: Adult; Aged; Aged, 80 and over; Apoptosis; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Lymphocytes; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; Neoplasm Invasiveness; Neoplasm Proteins; STAT3 Transcription Factor; Skin Neoplasms; Trans-Activators

PY - 2004

Y1 - 2004

N2 - A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages. In contrast, only sporadic and faint staining was observed in indolent lesions of patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL.

AB - A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages. In contrast, only sporadic and faint staining was observed in indolent lesions of patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL.

U2 - 10.1038/sj.leu.2403385

DO - 10.1038/sj.leu.2403385

M3 - Journal article

C2 - 15141228

VL - 18

SP - 1288

EP - 1295

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 7

ER -