title: Cks1 is required for tumor cell proliferation but not sufficient to induce hematopoietic malignancies.
abstract: The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27(Kip1) levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27(Kip1). To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo.
authors.affiliation: III. Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kratzat
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Nikolova
authors.forename: Cornelius
authors.initials: C
authors.lastname: Miething
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoellein
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schoeffmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Gorka
authors.forename: Elke
authors.initials: E
authors.lastname: Pietschmann
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Illert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Jonas
authors.initials: J
authors.lastname: Nilsson
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000378:metabolism*; D015151:Immunoblotting; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D012190:Retroviridae
chemical_list: D049452:Green Fluorescent Proteins; D042846:CDC2-CDC28 Kinases; C474110:Cks1 protein, mouse