Distinct promoters, subjected to epigenetic regulation, drive the expression of two clusterin mRNAs in prostate cancer cells.

The human clusterin (CLU) gene codes for several mRNAs characterized by different sequences at their 5' end. We investigated the expression of two CLU mRNAs, called CLU 1 and CLU 2, in immortalized (PNT1a) and tumorigenic (PC3 and DU145) prostate epithelial cells, as well as in normal fetal fibroblasts (WI38) following the administration of the epigenetic drugs 5-aza-2'-deoxycytidine (AZDC) and trichostatin A (TSA) given either as single or combined treatment (AZDC-TSA). Our experimental evidences show that: a) CLU 1 is the most abundant transcript variant.

Chapter 2: Clusterin (CLU): From one gene and two transcripts to many proteins.

Clusterin (CLU) has kept many researchers engaged for a long time since its first discovery and characterization in the attempt to unravel its biological role in mammals. Although there is a general consensus on the fact that CLU is supposed to play important roles in nearly all fundamental biological phenomena and in many human diseases including cancer, after about 10 years of work CLU has been defined as an "enigmatic" protein. This sense of frustration among the researchers is originated by the fact that, despite considerable scientific production concerning CLU, there is still a lack of basic information about the complex regulation of its expression.