Expression of Protein Kinase Cα and the MZF-1 and Elk-1 Transcription Factors in Human Bladder Transitional Cell Carcinoma Cells

Jou, Yeong Chin; Chiu, Yung Wei; Chen, Yieng How; Hwang, Jin Ming; Chao, Pei Yu; Shiu, Jiuan Jen; Hwang, Wen Hung; Liu, Jer Yuh; Hsu, Li Sung

doi:10.4077/cjp.2012.amm121

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…However, none of these studies have assessed the prognostic value of ELK1 or p-ELK1 expression. On the other hand, the expression levels of ELK1 [ 37 ] and p-ELK1 [ 38 ] have been determined in bladder cancer cell lines. Our immunohistochemical staining in bladder tissue microarrays (TMAs) showed that, compared with non-neoplastic urothelium, significant increases in the expression of ELK1 and p-ELK1 were observed in bladder tumor.…”

Section: Discussionmentioning

confidence: 99%

ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

et al. 2015

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Little is known about biological significance of ELK1, a transcriptional factor that activates downstream targets including c-fos proto-oncogene, in bladder cancer. Recent preclinical evidence also suggests the involvement of androgen receptor (AR) signaling in bladder cancer progression. In this study, we aim to investigate the functions of ELK1 in bladder cancer growth and their regulation by AR signals. Immunohistochemistry in bladder tumor specimens showed that the levels of phospho-ELK1 (p-ELK1) expression were significantly elevated in urothelial neoplasms, compared with non-neoplastic urothelium tissues, and were also correlated with AR positivity. Patients with p-ELK1-positive non-muscle-invasive and muscle-invasive tumors had significantly higher risks for tumor recurrence and progression, respectively. In AR-positive bladder cancer cell lines, dihydrotestosterone treatment increased ELK1 expression (mRNA, protein) and its nuclear translocation, ELK1 transcriptional activity, and c-fos expression, which was restored by an anti-androgen hydroxyflutamide. ELK1 silencing via short hairpin RNA (shRNA) resulted in decreases in cell viability/colony formation, and cell migration/invasion as well as an increase in apoptosis. Importantly, ELK1 appears to require activated AR to regulate bladder cancer cell proliferation, but not cell migration. Androgen also failed to significantly induce AR transactivation in ELK1-knockdown cells. In accordance with our in vitro findings, ELK1-shRNA expression considerably retarded tumor formation as well as its growth in xenograft-bearing male mice. Our results suggest that ELK1 plays an important role in bladder tumorigenesis and cancer progression, which is further induced by AR activation. Accordingly, ELK1 inhibition, together with AR inactivation, has the potential of being a therapeutic approach for bladder cancer.

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Section: Discussionmentioning

confidence: 99%

ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

et al. 2015

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“…Moreover, in vitro assays have indicated that overexpression of SRF in thyroid cancer cells enhances the expression level of c-Fos protein, cell migration, and invasiveness 20 . The role of MZF1 in thyroid cancer has never been investigated, however, it was involved in colorectal, cervical, and bladder carcinogenesis 21 22 23 .…”

Section: Discussionmentioning

confidence: 99%

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

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Chen

Elisei

et al. 2015

Sci Rep

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A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR = 1.36, 95%CI 1.20–1.53, p-value = 7.41 × 10−7) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16–1.44, p-value = 4.42 × 10−6). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend = 3.13 × 10−47). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.

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Expression of myeloid zinc finger 1 and the correlation to clinical aspects of oral squamous cell carcinoma

Yang

Chen

et al. 2015

Tumor Biol.

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The myeloid zinc finger 1 (MZF1) is a zinc finger transcription factor which regulates myeloid differentiation and oncogenesis. However, little information is available concerning the MZF1 expression in oral squamous cell carcinoma (OSCC) and its correlation with patients' prognosis. We detected the expression of MZF1 in 274 patients with OSCC using tissue microarrays (TMAs) and evaluated the associations between nuclear MZF1 expression and the clinical parameters of OSCC patients. We found that nuclear MZF1 expression was present in 190/274 (69.3 %) cases, and loss of nuclear expression of MZF1 was associated with more advanced clinical stages (p = 0.011) and larger tumor size (p = 0.002), but not associated with positive lymph node metastasis and distal metastasis. Importantly, tongue squamous cell carcinomas (SCC) patients with negative nuclear MZF1 expression had significantly worse overall survival rates (log-rank test, p = 0.028). In conclusion, our results revealed that the loss of nuclear expression of MZF1 in OSCC samples can predict the progression of OSCC and the survival of OSCC patients in Taiwan.

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Expression of Protein Kinase Cα and the MZF-1 and Elk-1 Transcription Factors in Human Bladder Transitional Cell Carcinoma Cells

Cited by 3 publications

References 23 publications

ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

Expression of myeloid zinc finger 1 and the correlation to clinical aspects of oral squamous cell carcinoma

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