title: Differential transformation capacity of Src family kinases during the initiation of prostate cancer.
abstract: Src family kinases (SFKs) are pleiotropic activators that are responsible for integrating signal transduction for multiple receptors that regulate cellular proliferation, invasion, and metastasis in a variety of human cancers. Independent groups have identified increased expression of individual SFK members during prostate cancer progression, raising the question of whether SFKs display functional equivalence. Here, we show that Src kinase, followed by Fyn kinase and then Lyn kinase, exhibit ranked tumorigenic potential during both paracrine-induced and cell-autonomous-initiated prostate cancer. This quantitative variation in transformation potential appears to be regulated in part by posttranslational palmitoylation. Our data indicate that development of inhibitors against specific SFK members could provide unique targeted therapeutic strategies.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Houjian
authors.initials: H
authors.lastname: Cai
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Smith
authors.forename: Sanaz
authors.initials: S
authors.lastname: Memarzadeh
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases