Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma

TY - JOUR

T1 - Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma

AU - Kamstrup, Maria R

AU - Biskup, Edyta

AU - Manfè, Valentina

AU - Savorani, Cecilia

AU - Liszewski, Walter

AU - Wirén, Johan

AU - Specht, Lena

AU - Gniadecki, Robert

PY - 2017/1/2

Y1 - 2017/1/2

N2 - The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism.

AB - The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism.

KW - Journal Article

U2 - 10.1080/10428194.2016.1180681

DO - 10.1080/10428194.2016.1180681

M3 - Journal article

C2 - 27181628

SN - 1042-8194

VL - 58

SP - 171

EP - 178

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 1

ER -