PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

Hsieh, Yi‐Hsien; Wu, Trang Tiau; Tsai, Jer‐Chia; Huang, Chih Yang; Hsieh, Yih Shou; Liu, Jer Yuh

doi:10.1016/j.bbrc.2005.11.015

Cited by 50 publications

(58 citation statements)

References 26 publications

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“…In later studies, it was found that overexpression of MZF1 inhibits apoptosis and promotes oncogenesis (6,7), and silencing of MZF1 with antisense oligonucleotides was shown to reduce tumor growth (9). However, the mechanisms by which MZF1 exerts an oncogenic potential are unknown except that it can regulate protein kinase C α expression (8). Moreover, data suggesting a tumorigenic potential of MZF1 have been controversial (43).…”

Section: Discussionmentioning

confidence: 99%

“…Differential expression of MZF-1 interferes with hematopoietic cell differentiation and proliferation (3)(4)(5) and is associated with the antiapoptotic, oncogenic transformation of cell lines (6,7). MZF1 transcriptionally regulates protein kinase C α in human hepatocellular carcinoma (8), which is an important family of signaling molecules that regulate cell proliferation, differentiation, transformation, and apoptosis. MZF1 antisense oligonucleotide-pretreated SK-Hep-1 human hepatocellular carcinoma cells showed reduced protein kinase C expression, and antisense-treated cells s.c. implanted into nude mice exhibited lower tumor growth and prolonged formation time (9).…”

Section: Introductionmentioning

confidence: 99%

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Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Mudduluru

Vajkoczy

Allgayer

2010

Molecular Cancer Research

118

129

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Myeloid zinc finger 1 (MZF1) is a member of the SCAN domain family transcription factors that form dimers through their highly conserved SCAN motifs. Silencing of MZF1 inhibits cell proliferation, and abnormal expression of MZF1 results in cancer development. However, a potential role of MZF1 in metastasis remains unclear. Axl is a receptor tyrosine kinase and was first identified as a transforming gene in chronic myeloid leukemia. Axl overexpression induces proliferation, migration, and invasion and is highly expressed in different human cancers. In this study, we show that overexpression of MZF1 induces migration and invasion in colorectal (Rko, SW480) and cervical (HeLa) cancer cells. In addition, we show that MZF1 binds to the Axl promoter, transactivates promoter activity, and enhances Axl-mRNA and protein expression in a dose-dependent manner. In vitro, sh-RNA knockdown of Axl reduced MZF1-induced migration and invasion in HeLa and Rko cells (P = 0.05). Additionally, Rko cells overexpressing MZF1 showed increased tumor formation and liver metastasis in the chicken-embryo-metastasis assay in vivo. Furthermore, the expression of MZF1 and Axl was significantly higher in resected colorectal tumors compared with corresponding normal tissues (P = 0.02; P = 0.05), and MZF1 expression was positively correlated with Axl gene expression in tumor tissues (P < 0.01). Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. Mol Cancer Res; 8(2); 159-69. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Mudduluru

Vajkoczy

Allgayer

2010

Molecular Cancer Research

118

129

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“…In our previous study, PKCa has been found to be highly expressed in the poorly differentiated human hepatocellular carcinoma (HCC) cell lines (SK-Hep-1 and HA22T/VGH) as compared with the well-differentiated ones (PLC/PRF/5, Hep3B, and HepG2; ref. 24). To determine the role of MAPKs in PKCamediated HCC migration and invasion, we investigated the signal pathways selectively activated by PKCa in the SK-Hep-1 and HA22T/VGH cells.…”

Section: Introductionmentioning

confidence: 99%

p38 Mitogen-Activated Protein Kinase Pathway Is Involved in Protein Kinase Cα–Regulated Invasion in Human Hepatocellular Carcinoma Cells

Hsieh¹,

Huang

et al. 2007

Cancer Research

Self Cite

101

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Protein kinase CA (PKCA) has been suggested to play an important role in tumorigenesis, invasion, and metastasis. In this study, we investigated the signal pathways selectively activated by PKCA in human hepatocellular carcinoma (HCC) cells to determine the role of mitogen-activated protein kinases (MAPK) in PKCA-mediated HCC migration and invasion. A stable SK-Hep-1 cell clone (siPKCA-SK) expressing DNA-based small interfering RNA (siRNA) PKCA was established and was then characterized by cell growth, migration, and invasion. The expression of PKCA was decreased in siPKCA-SK, and cell growth, migration, and invasion were reduced. These changes were associated with the decrease in p38 MAPK phosphorylation level, but not in c-jun-NH 2 -kinase-1/2 (JNK-1/2) and extracellular signal-regulated kinase-1/2 (ERK-1/2). This phenomenon was confirmed in the SK-Hep-1 cells treated with antisense PKCA olignucleotide. The p38 MAPK inhibitor SB203580 or dominant negative p38 mutant plasmid (DN-p38) was used to evaluate the dependency of p38 MAPK in PKCA-regulated migration and invasion. Attenuation of cell migration and invasion was revealed in the SKHep-1 cells treated with the SB203580 or DN-p38, but not with ERK-1/2 inhibitor PD98059 or JNK-1/2 inhibitor SP600125. Overexpression of constitutively active MKK6 or PKCA may restore the inactivation of p38 and the attenuation of cell migration and invasion in siPKCA-SK. Similar findings were observed in the stable HA22T/VGH cell clone expressing siRNA PKCA. This study provides new insight into the role of p38 MAPK in PKCA-mediated malignant phenotypes, especially in PKCA-mediated cancer cell invasion, which may have valuable implications for developing new therapies for some PKCAoverexpressing cancers. [Cancer Res 2007;67(9):4320-7]

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“…Furthermore tumor stromal cells also induced increased expression of ELK1 in T47D cells in vitro and in vivo. ELK1, a member of the ets oncogene family, promotes tumor progression, and is critical to regulation of cell proliferation and apoptosis [38]. While ELK1 expression was increased in vitro (sixfold increase), the level of increase was markedly higher in vivo (54-fold).…”

Section: Discussionmentioning

confidence: 98%

Influence of stromal–epithelial interactions on breast cancer in vitro and in vivo

Potter

Dwyer

Hartmann

et al. 2011

Breast Cancer Res Treat

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Stromal cell-secreted chemokines including CCL2 have been implicated in the primary tumor microenvironment, as mediators of tumor cell migration, proliferation, and angiogenesis. Expression of CCL2 and its principal receptor CCR2 was analyzed by RQ-PCR in primary tumor cells and breast cancer cell lines. Breast cancer cell lines (MDA-MB-231, T47D) were co-cultured directly on a monolayer of primary breast tumor and normal stromal cells, retrieved using EpCAM+ magnetic beads, and changes in expression of CCL2, CCR2, MMP11, ELK1, VIL2, and Ki67 detected by RQ-PCR. Epithelial cell migration and proliferation in response to stromal cell-secreted factors was also analyzed. In vivo, tumor xenografts were formed by co-injecting T47D cells with primary tumor stromal cells. Following establishment, tumors were harvested and digested, epithelial cells retrieved and analyzed by RQ-PCR. Whole tumor tissue was also analyzed by immunohistochemistry for CD31 and the VIL2 encoded protein Ezrin. Tumor stromal cells expressed significantly higher levels of CCL2 than normal cells, with no CCR2 expression detected. Primary epithelial cells and breast cancer cell lines expressed elevated CCL2, with relative expression of CCR2 found to be higher than the ligand. Interaction of breast cancer epithelial cells with primary tumor, but not normal stromal cells, stimulated increased expression of CCL2 (8-fold), ELK1 (6-fold), VIL2 (6-fold), and MMP11 (17-fold). Factors secreted by stromal cells, including CCL2, stimulated a significant increase in epithelial cell migration, with no effect on cell proliferation in vitro observed. In vivo, the presence of stromal cells resulted in tumors of increased volume, mediated at least in part through neoangiogenesis demonstrated by immunohistochemistry (CD31). Admixed tumor xenografts exhibited increased expression of Ki67, MMP11, VIL2, and ELK1. Elevated Ezrin protein was also detected, with increased cytoplasmic localization. The results presented highlight mechanisms through which breast cancer epithelial cells can harness stromal cell biology to support tumor progression.

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PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

Cited by 50 publications

References 26 publications

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

p38 Mitogen-Activated Protein Kinase Pathway Is Involved in Protein Kinase Cα–Regulated Invasion in Human Hepatocellular Carcinoma Cells

Influence of stromal–epithelial interactions on breast cancer in vitro and in vivo

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