The epigenetic basis for the aberrant expression of kallikreins in human cancers.
The tissue kallikrein gene family consists of 15 genes tandemly arranged on human chromosome 19q13.4. Most kallikrein genes are characterized by aberrant expression patterns in various human cancers, a feature that makes them ideal cancer biomarkers. In the present study, we investigated the effect of the epigenetic drug compound 5-aza-2'-deoxycytidine on the expression of downregulated kallikrein genes in prostate, breast, and ovarian cancer cell lines. Reactivation of multiple kallikrein genes was observed, although some of these genes do not contain CpG islands in their genomic sequence. Epigenetic regulation provides a new mechanism for the pharmacological modulation of kallikreins in human cancers with putative therapeutic implications.
Pampalakis
Georgios
G
Department of Pharmacy, School of Health Sciences, University of Patras, GR-26500 Rion-Patras, Greece, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada. geopamp@upatras.gr
Diamandis
Eleftherios P
EP
Sotiropoulou
Georgia
G
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics
D000077209:Decitabine; D007610:Kallikreins; D001374:Azacitidine