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.
| Original language | English |
|---|---|
| Pages (from-to) | 23-30 |
| Number of pages | 8 |
| Journal | Hematological Oncology |
| Volume | 27 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2009 |
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Keywords
- Cell line
- Enzastaurin
- Gene expression profiling
- Molecular pathway
- Multiple myeloma
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Molecular targeting of the PKC-β inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression. / Verdelli, Donata; Nobili, Lucia; Todoerti, Katia; Intini, Daniela; Cosenza, Maria; Civallero, Monica; Bertacchini, Jessika; Deliliers, Giorgio Lambertenghi; Sacchi, Stefano; Lombardi, Luigia; Neri, Antonino.
In: Hematological Oncology, Vol. 27, No. 1, 2009, p. 23-30.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular targeting of the PKC-β inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression
AU - Verdelli, Donata
AU - Nobili, Lucia
AU - Todoerti, Katia
AU - Intini, Daniela
AU - Cosenza, Maria
AU - Civallero, Monica
AU - Bertacchini, Jessika
AU - Deliliers, Giorgio Lambertenghi
AU - Sacchi, Stefano
AU - Lombardi, Luigia
AU - Neri, Antonino
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Cell line
KW - Enzastaurin
KW - Gene expression profiling
KW - Molecular pathway
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=65249135021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249135021&partnerID=8YFLogxK
U2 - 10.1002/hon.875
DO - 10.1002/hon.875
M3 - Article
C2 - 18759374
AN - SCOPUS:65249135021
VL - 27
SP - 23
EP - 30
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 1
ER -