title: Frequent alterations in the expression of serine/threonine kinases in human cancers.
abstract: Protein kinases constitute a large family of regulatory enzymes involved in the homeostasis of virtually every cellular process. Subversion of protein kinases has been frequently implicated in malignant transformation. Within the family, serine/threonine kinases (STK) have received comparatively lesser attention, vis-a-vis tyrosine kinases, in terms of their involvement in human cancers. Here, we report a large-scale screening of 125 STK, selected to represent all major subgroups within the subfamily, on nine different types of tumors ( approximately 200 patients), by using in situ hybridization on tissue microarrays. Twenty-one STK displayed altered levels of transcripts in tumors, frequently with a clear tumor type-specific dimension. We identified three patterns of alterations in tumors: (a) overexpression in the absence of expression in the normal tissues (10 kinases), (b) overexpression in the presence of expression by normal tissues (8 kinases), and (c) underexpression (3 kinases). Selected members of the three classes were subjected to in-depth analysis on larger case collections and showed significant correlations between their altered expression and biological and/or clinical variables. Our findings suggest that alteration in the expression of STK is a relatively frequent occurrence in human tumors. Among the overexpressed kinases, 10 were undetectable in normal controls and are therefore ideal candidates for further validation as potential targets of molecular cancer therapy.
authors.affiliation: Istituto FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Capra
authors.forename: Paolo Giovanni
authors.initials: PG
authors.lastname: Nuciforo
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.forename: Micaela
authors.initials: M
authors.lastname: Quarto
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Mikhail L
authors.initials: ML
authors.lastname: Gishizky
authors.forename: Giulio F
authors.initials: GF
authors.lastname: Draetta
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
mesh_terms: D018076:DNA, Complementary / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013698:Templates, Genetic
chemical_list: D018076:DNA, Complementary; D017346:Protein Serine-Threonine Kinases