title: Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma.
abstract: 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.
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Kamstrup
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.
authors.forename: Edyta
authors.initials: E
authors.lastname: Biskup
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.
authors.forename: Valentina
authors.initials: V
authors.lastname: Manfè
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Savorani
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.
authors.forename: Walter
authors.initials: W
authors.lastname: Liszewski
authors.affiliation: b Department of Oncology , Skaane University Hospital , Lund , Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Wirèn
authors.affiliation: c Department of Oncology , Rigshospitalet , Copenhagen , Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: a Department of Dermatology , Bispebjerg Hospital , Copenhagen , Denmark.|d Division of Dermatology , University of Alberta , Edmonton , Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D051881:Receptor, Notch1
keywords: Chemotherapy; Notch1; cutaneous T-cell lymphoma