Evaluation of caspase-3 and caspase-8 deregulation in tongue squamous cell carcinoma, based on immunohistochemistry and computerised image analysis

Andressakis, D; Lazaris, Andreas C.; Tsiambas, Evangelos; Kavantzas, N; Rapidis, Alexander D.; Patsouris, Efstratios

doi:10.1017/s0022215108002636

Cited by 23 publications

(36 citation statements)

References 29 publications

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“…Since we did not correlate the expression levels of MCPH1 and CASP3 in OSCC samples, we performed a literature search to find if CASP3 expression has been reported in oral cancer. We found that CASP3 protein has been shown to be downregulated in 79/87 (90.80%) of tongue squamous cell carcinoma [43]. In contrary to this study, overexpression of CASP3 (protein) has been reported in a study using 39 samples of normal oral epithelium and 54 oral squamous cell carcinomas [42].…”

Section: Discussioncontrasting

confidence: 88%

Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

et al. 2013

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Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.

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Section: Discussioncontrasting

confidence: 88%

Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

et al. 2013

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“…Activation of Caspase-3 is a critical event during cell apoptosis, which can be activated by upstream signaling from, for example, Caspase-8 and -9 (Janicke, 2008). However, simultaneous deregulation of Caspase-3 and -8 is a frequent event in tongue squamous cell carcinoma (Andressakis et al, 2008). Activation of Caspase-3, which is predominantly down-regulated, may be a crucial process for induction of apoptosis and response to therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

DAPT Enhances the Apoptosis of Human Tongue Carcinoma Cells

et al. 2009

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“…Regarding the roles of caspase-3/8/9 in cancer, impaired expression of caspase-8 and caspase-3 can promote tumor formation and progression and treatment resistance in several types of cancer, including oral cancer [14, 15]. However, the expression levels of caspase-8 and caspase-9 are higher in oral squamous carcinoma cells (OSCCs) than in the adjacent normal cells [16].…”

Section: Introductionmentioning

confidence: 99%

Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma

et al. 2017

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Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p<0.001). The expression level of caspase-8 in tumors was elevated in patients with lymph node invasion. Moreover, positive expression of cleaved caspase-3 was associated with shorter disease-free survival (DFS) in OTSCC patients with moderate differentiation and lymph node invasion. Combination of either positive cleaved caspase-3 or higher caspase-3 expression or both was associated with poor DFS. Interestingly, stratification analysis showed that co-expression levels of positive cleaved caspase-3 or/and higher caspase-3 were associated with better disease-specific survival in patients with advanced stages of the disease, such as large tumor size and lymph node invasion, whereas it was associated with poor DFS in OTSCC patients with moderate cell differentiation and small tumor size. Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status.

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Evaluation of caspase-3 and caspase-8 deregulation in tongue squamous cell carcinoma, based on immunohistochemistry and computerised image analysis

Abstract: Simultaneous deregulation of caspase-8 and -3 is a frequent event in tongue squamous cell carcinoma. Activation of caspase-3, which is predominantly down-regulated, may be a crucial process for induction of apoptosis and response to therapeutic strategies.

Cited by 23 publications

References 29 publications

Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

DAPT Enhances the Apoptosis of Human Tongue Carcinoma Cells

Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma

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