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.

Clusterin transcript variants expression in thyroid tumor: a potential marker of malignancy?

“…Specifically, the neoplastic transformation may manifest itself with the alteration of synthesis of the two CLU transcript variants with a dominance of CLU2 over CLU1, resulting in the promotion of transformed cell survival. This hypothesis is in agreement with previous studies suggesting that the survival of cancer cells is related to over-expression of CLU2 and down-regulation of CLU1 transcripts [ 21 ].…”

“…These inspections revealed multiple possible CLU transcript variants, two of which identified by the Signature ID [ 29 ] c7175b345e:9 and 1057fea355:9, overlapping to the sequences of the NCBI database with accession number NM_001831, CLU1 and NR_038335, CLU2. These two variants all contain nine exons, and each of them presents a unique exon 1 and shares the remaining 2–9 exons [ 21 ]. Although the CLU1 transcript variant was not present in other cancer tissues [ 11 , 30 ] the reason why it is taken into consideration is because it stood out by having substantially more sequence support than the others in the ASPicDB in silico analysis.…”

“…By RT-PCR analysis followed by sequencing experiments, the two CLU transcript variants were found to be expressed in the human thyroid tissues. Moreover, by using the specific CLU primers [ 21 ], no additional bands were detected except the two variant-specific RT-PCRs (data not shown).…”

The Cellular and Molecular Biology of the Iris, an Overlooked Tissue

“…11 Clusterin appears to be subjected to post-transcriptional regulation. 12 An analysis (at writing) of the NEI bank libraries of eye tissues (http://neibank.nei.nih.gov/index.shtml) showed that the iris was the tissue where clusterin was the most abundantly expressed gene. Clusterin ranked first in the iris, 15 th on the lens, 27 th in cornea, and 29 th in the retina.…”

“…14 This finding would be consistent with the presence of a post-transcriptional regulation for this gene, which has been described in the endometria. 12 …”