RESUMO
Protocadherin-10 (PCDH10) which is located at 4q28.3, is a member of the cadherin superfamily of cell adhesion molecules. PCDH10 is broadly expressed in normal adult, but nearly undetectable in multiple myeloma (ΜΜ) tissues and cell lines. Its promoter methylation was detected in virtually all the silenced or downregulated cell lines. The silencing of PCDH10 could be reversed by pharmacological demethylation, indicating a methylation-mediated mechanism. In the current study, we investigated 44 patients (23 females, 21 males), 77.27% (34/44) of whom presented high methylation of PCDH10. We found no associations between promoter hypermethylation and gender or age at the time of initial diagnosis. We also examined the role of PCDH10 as a mediator of MM cell proliferation, cell cycle progression, and its involvement in angiogenesis. Our results demonstrate that the PCDH10 gene is a target for epigenetic silencing in MM and provide a link between the dysregulation of angiogenesis and DNA methylation.
Assuntos
Caderinas/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica , Adulto , Idoso , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Epigênese Genética , Feminino , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Regiões Promotoras Genéticas , ProtocaderinasRESUMO
Phospholipase C δ1 (PLCD1), is located at the important tumor suppressor locus 3p22. It encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. PLCD1 has been studied in some human solid tumors relating to the CpG island methylation of the gene promoter as a functional tumor suppressor. However, no such information is available in chronic myeloid leukemia (CML). In this study, we investigated PLCD1 expression in the CML K562 cell line (0/1) and 15% (2/13) of bone marrow mononuclear cells with CML by using semi-quantitative PCR. The CpG island (CGI) methylation status of the PLCD1 promoter was detected in K562 (0/1) and 56% (23/41) of CML patients by methylation-specific PCR (MSP), but not in the normal adult bone marrow mononuclear cells. Furthermore, the DNA demethylation agent 5'-aza-2'deoxycytidine restored the expression of PLCD1 in K562 cells. Functional studies showed that ectopic expression of PLCD1 in K562 cells was able to dramatically inhibit their colony formation and induce cell cycle G1 arrest, suggesting that PLCD1 acts as a functional tumor suppressor and may serve as a biomarker for possible early detection and prognosis of CML.