title: Cdk9 regulates neural differentiation and its expression correlates with the differentiation grade of neuroblastoma and PNET tumors.
abstract: Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The Cdk9/Cyclin T complex appears to be involved in regulating several physiological processes. Recently, Cdk9 has been identified as a regulator of the differentiation program of several cell types, such as muscle cells, monocytes and lymphocytes, suggesting that it may have a function in controlling specific differentiative pathways. We analyzed whether Cdk9 and Cyclin T1 may be involved in the regulation of neuron and astrocyte differentiation. Cdk9 and Cyclin T1 expression levels were monitored during the differentiation program of neuroblastoma and astrocytoma cell lines. Our results suggest that Cdk9/Cyclin T1 complex may be required for neuron differentiation induced by retinoic acid, because the expression level of the complex varies during differentiation, but no significant changes were observed in its expression in the astrocytoma cell line. In addition, the expression of Cdk9 and Cyclin T1 was evaluated by immunohistochemistry in samples of neuroblastoma, PNET (Primary Neuroectodermal Tumor) and astrocytoma tumors of different grades, in order to assess whether there was a correlation between Cdk9 expression and tumor grading. Our results show that in neuroblastoma and PNET tumor samples Cdk9 is more expressed the more differentiated the tumor is. Conversely, no significant alteration of Cdk9 expression was observed in astrocytoma tumor samples of different grades, thus confirming the results obtained for the cell lines.
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Alessandro
authors.initials: A
authors.lastname: D'Amuri
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Angeloni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Leucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D012333:RNA, Messenger; D014212:Tretinoin; D042863:Cyclin-Dependent Kinase 9