title: Regulation of the expression of CLU isoforms in endometrial proliferative diseases.
abstract: Clusterin (CLU) is a nearly ubiquitous multifunctional protein synthesized in different functionally divergent isoforms, sCLU and nCLU, playing a crucial role by keeping a balance between cell proliferation and death. Studying in vivo CLU expression we found a higher mRNA expression both in neoplastic and hyperplastic tissues in comparison to normal endometria; in particular, by RT-qPCR we demonstrated an increase of the specific sCLU isoform in the neoplastic and hyperplastic endometrial diseases. On the contrary, no CLU increase was detected at the protein level. The CLU gene transcriptional activity was upregulated in the hyperplastic and neoplastic tissues, indicating the existence of a fine post-trans-criptional regulation of CLU expression possibly responsible for the protein decrease in the malignant disease. A specific CLU immunoreactivity was present in all the endometrial glandular cells in comparison to the other cellular compartments where CLU immunoreactivity was lower or absent. In conclusion, our results suggest the existence of a complex regulatory mechanism of CLU gene expression during the progression from normal to malignant cells, possibly contributing to endometrial carcinogenesis. Moreover, the specific alteration of the sCLU:nCLU ratio associated with the pathological stage, suggests a possible usage of CLU as molecular biomarker for the diagnosis/prognosis of endometrial proliferative diseases.
authors.affiliation: Institute of Biomedical Technologies, ITB-CNR, I-70126 Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fuzio
authors.forename: Alessio
authors.initials: A
authors.lastname: Valletti
authors.forename: Anna
authors.initials: A
authors.lastname: Napoli
authors.forename: Grazia
authors.initials: G
authors.lastname: Napoli
authors.forename: Gennaro
authors.initials: G
authors.lastname: Cormio
authors.forename: Luigi
authors.initials: L
authors.lastname: Selvaggi
authors.forename: Sabino
authors.initials: S
authors.lastname: Liuni
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.forename: Elda
authors.initials: E
authors.lastname: Perlino
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D051152:Clusterin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012016:Reference Values
chemical_list: D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D020033:Protein Isoforms