The protein kinase C (PKC) pathway has been shown to play a role in the regulation of cell proliferation in several haematological malignancies, including multiple myeloma (MM). Recent data have shown that a PKC inhibitor, enzastaurin, has antiproliferative and proapoptotic activity in a large panel of human myeloma cell lines (HMCLs). In order to further characterise the effect of enzastaurin in MM, we performed gene expression profiling of enzastaurin-treated KMS-26 cell line. We identified 62 upregulated and 32 downregulated genes that are mainly involved in cellular adhesion (CXCL12, CXCR4), apoptosis (CTSB, TRAF5, BCL2L1), cell proliferation (IGF1, GADD45A, BCMA (B-cell maturation antigen), CDC20), transcription regulation (MYC, MX11, IRF4), immune and defence responses. Subsequent validation by Western blotting of selected genes in four enzastaurin-treated HMCLs was consistent with our microarray analysis. Our data indicate that enzastaurin may affect important processes involved in the proliferation and survival of malignant plasma cells as well as in their interactions with the bone marrow microenvironment and provide a preclinical rationale for the potential role of this drug in the treatment of MM.

Molecular targeting of the PKC-β inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression / Verdelli, D; Nobili, L; Todoerti, K; Intini, D; Cosenza, Maria; Civallero, Monica; Bertacchini, Jessika; Deliliers, Gl; Sacchi, Stefano; Lombardi, L; Neri, A.. - In: HEMATOLOGICAL ONCOLOGY. - ISSN 0278-0232. - STAMPA. - 27:1(2009), pp. 23-30. [10.1002/hon.875]

Molecular targeting of the PKC-β inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression

COSENZA, Maria;CIVALLERO, Monica;BERTACCHINI, Jessika;SACCHI, Stefano;
2009

Abstract

The protein kinase C (PKC) pathway has been shown to play a role in the regulation of cell proliferation in several haematological malignancies, including multiple myeloma (MM). Recent data have shown that a PKC inhibitor, enzastaurin, has antiproliferative and proapoptotic activity in a large panel of human myeloma cell lines (HMCLs). In order to further characterise the effect of enzastaurin in MM, we performed gene expression profiling of enzastaurin-treated KMS-26 cell line. We identified 62 upregulated and 32 downregulated genes that are mainly involved in cellular adhesion (CXCL12, CXCR4), apoptosis (CTSB, TRAF5, BCL2L1), cell proliferation (IGF1, GADD45A, BCMA (B-cell maturation antigen), CDC20), transcription regulation (MYC, MX11, IRF4), immune and defence responses. Subsequent validation by Western blotting of selected genes in four enzastaurin-treated HMCLs was consistent with our microarray analysis. Our data indicate that enzastaurin may affect important processes involved in the proliferation and survival of malignant plasma cells as well as in their interactions with the bone marrow microenvironment and provide a preclinical rationale for the potential role of this drug in the treatment of MM.
2009
27
1
23
30
Molecular targeting of the PKC-β inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression / Verdelli, D; Nobili, L; Todoerti, K; Intini, D; Cosenza, Maria; Civallero, Monica; Bertacchini, Jessika; Deliliers, Gl; Sacchi, Stefano; Lombardi, L; Neri, A.. - In: HEMATOLOGICAL ONCOLOGY. - ISSN 0278-0232. - STAMPA. - 27:1(2009), pp. 23-30. [10.1002/hon.875]
Verdelli, D; Nobili, L; Todoerti, K; Intini, D; Cosenza, Maria; Civallero, Monica; Bertacchini, Jessika; Deliliers, Gl; Sacchi, Stefano; Lombardi, L; ...espandi
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/608821
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 19
social impact