title: Dynamic heterogeneity of proteomic expression in human cancer cells does not affect Cdk1/Cdk4 co-expression.
abstract: Tumour heterogeneity is becoming increasingly important as an obstacle to genomic and proteomic technologies designed to improve the diagnosis and treatment of human cancer. In a panel of 19 human in-vitro cancer cell lines, we show marked heterogeneity of proteomic expression of key genes responsible for the control of cell division and death. Patterns of expression of these proteins were unique for each cell line. In addition, dynamic heterogeneity of proteomic expression of Cyclin D1, Cdk1, Cdk4 and even actin was detected. The relative levels of each protein fluctuated independently from experiment to experiment separated only by short passages in tissue culture. Cdk1 and Cdk4 proteomic co-expression (Seabra, 2007) was not, however, affected by dynamic heterogeneity, or, in 4 cell lines, by treatment with D0.1 doses of CDDP. Cdk1/Cdk4 may thus provide a complex molecular target for anti-cancer drug development which is unaffected by tumour heterogeneity and is not disrupted by conventional chemotherapy.
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton, UK. H.Warenius@soton.ac.uk
authors.forename: Hilmar
authors.initials: H
authors.lastname: Warenius
authors.forename: Amanda
authors.initials: A
authors.lastname: Howarth
authors.forename: Laurence
authors.initials: L
authors.lastname: Seabra
authors.forename: Leto
authors.initials: L
authors.lastname: Kyritsi
authors.forename: Roisin
authors.initials: R
authors.lastname: Dormer
authors.forename: Shanez
authors.initials: S
authors.lastname: Anandappa
authors.forename: Carole
authors.initials: C
authors.lastname: Thomas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D019938:Cyclin D1; D016203:CDC2 Protein Kinase; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4