Expression of Bcl‐2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma

Coutinho‐Camillo, Cláudia Malheiros; Lourenço, Sílvia Vanessa; Nishimoto, Inês Nobuko; Kowalski, Luiz Paulo; Soares, Fernando Augusto

doi:10.1111/j.1365-2559.2010.03621.x

Cited by 40 publications

(29 citation statements)

References 40 publications

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“…On the contrary to previous reports Coutinho-Camillo et al, found that expression of Bcl-2 in HNSCC was not significantly associated with any of the clinicopathological parameters. This difference in results could be explained by the large number of cases (229) included in their study [58].…”

Section: Archives In Cancer Research Issn 2254-6081mentioning

confidence: 84%

Immunohistochemical Study of CD68, CD3 and Bcl-2 and their Role in Progression and Prognosis of Head and Neck Squamous Cell Carcinoma

Helal¹,

Wahba²

2016

Arch Can Res

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Head and neck squamous cell carcinoma is diagnosed at late stages. The prevalence of metastatic lesions directly correlates with poor patient outcome. The progression to metastatic disease requires changes in the tumor microenvironment. Within the microenvironment, infiltrating immune cells facilitate the spread of tumor cells. Tumor-infiltrating lymphocytes play an important role in the response of tumors to therapy. Tumor-associated macrophages are the main cellular component in stroma of many tumors. The goal of cancer treatment is to abolish cell proliferation and to induce aptoptosis. Apoptosis is a key mechanism of tumor cell elimination. The Bcl2 protein itself is a product of a proto-oncogene and has an antiapoptotic action. The study used immunohistochemical staining of CD68, CD3, Bcl2 to measure macrophages, lymphocytes and evaluate apoptosis in 25 included cases; 5 cases of non specific dermatitis, 5 normal skin and 15 head and neck squamous cell carcinoma (HNSCC) graded into 5 well, 5 moderately and 5 poorly differentiated. CD68+ve macrophages were significantly higher in moderately differentiated HNSCC than well differentiated tumors. Poorly differentiated showed significantly lower CD68+ve macrophages than moderately differentiated tumors. CD3 +ve lymphocytes were significantly higher in well differentiated followed by moderate and poorly differentiated. CD3+ve lymphocytes were significantly higher in cases of dermatitis than HNSCC cases. Poorly differentiated SCC showed higher Bcl2 positivity followed by moderately differentiated. Well differentiated SCC showed the least Bcl2 positivity. This difference was significant. Our results showed tumor infiltrating macrophage and lymphocyte can predict the progression and prognosis of HNSCCs and the involvement of Bcl2 in HNSCC tumorigenesis.

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Section: Archives In Cancer Research Issn 2254-6081mentioning

confidence: 84%

Immunohistochemical Study of CD68, CD3 and Bcl-2 and their Role in Progression and Prognosis of Head and Neck Squamous Cell Carcinoma

Helal¹,

Wahba²

2016

Arch Can Res

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“…Alterations in the expression levels of apoptosis-related proteins have been reported in several cancers, including oral cancer [14][15][16]. In this study, by tissue microarray (TMA) analysis of 229 oral squamous cell carcinoma (OSCC) cases, the expression profiles of 23 apoptotic proteins were examined and a hierarchical cluster analysis was performed.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the expression of 23 proteins, our group have demonstrated that decreased expression of caspase-3 correlates with lymph node metastasis, lower caspase-7 levels are associated with disease-free survival in oral cancer, high Bim-Long expression is linked to overall survival and that elevated PUMA levels are associated with disease-free survival in oral cancer patients [15,16]. Elevated expression of Apaf-1 and survivin is associated with the absence of embolization, and the expression of Smac/DIABLO and cytochrome c is not significantly associated to any clinicopathological characteristic (unpublished results).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1, Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA, Apaf-1, caspase-2, caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, Smac/DIA-BLO, cytochrome c, and survivin was examined in OSCC tissue samples in a TMA [14,15]. Immunostaining was performed on two tissue slides from different cores of the same sample.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The primary function of apoptosis is to eliminate senescent or altered cells that are useless or harmful to a multicellular organism. Altered expression levels of apoptosis-related proteins have been reported in several cancers, including OSCC [14][15][16]. The development of resistance to apoptosis is a hallmark of malignant cells, enabling them to survive, despite apoptosis-inducing environmental signals and the loss of normal survival signals [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases

et al. 2017

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Background: Oral squamous cell carcinoma (OSCC) is the eighth most prevalent cancer worldwide. In recent large-scale studies, by immunohistochemistry and cluster analysis, several markers were associated with patient survival in various tumors. The aim of this study was to analyze the expression profiles of 23 proteins that have been linked to the inhibition (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1, and survivin) and promotion (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA, Apaf-1, caspase-2, caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, Smac/DIABLO, and cytochrome c) of apoptosis in OSCC. Methods: Two-hundred and twenty nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analyzed, and the results were quantified on an automated imaging system. The data were analyzed using a random forest clustering method.

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DIDS inhibits overexpression BAK1‐induced mitochondrial apoptosis through GSK3β/β‐catenin signaling pathway

Yang

Tang

et al. 2018

Journal Cellular Physiology

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Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway. The results showed overexpression BAK1 in 293T cells induced mitochondrial apoptosis accompanied by increasing the expression levels of cleaved caspase-9, -3, poly (ADP-ribose) polymerase (PARP) and reducing the MMP. Furthermore, overexpression BAK1 decreased the expression levels of Ser9-GSK3β and β-catenin. In addition, lithium chloride (LiCl), an activator of Wnt/β-catenin signaling pathway, markedly attenuated overexpression BAK1-induced mitochondrial apoptosis by restoring the expression levels of Ser9-GSK3β and β-catenin. Finally, DIDS absolutely abolished overexpression BAK1-mediated mitochondrial apoptosis through recovering the expression levels of Ser9-GSK3β and β-catenin. Taken together, our results reveal that DIDS blocks overexpression BAK1-induced mitochondrial apoptosis through GSK3β/β-catenin pathway.

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Expression of Bcl‐2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma

Abstract: Our results showed the involvement of the Bcl-2 family of proteins in OSCC tumorigenesis and suggest that the expression of apoptotic molecules might be used as a prognostic indicator for OSCC.

Cited by 40 publications

References 40 publications

Immunohistochemical Study of CD68, CD3 and Bcl-2 and their Role in Progression and Prognosis of Head and Neck Squamous Cell Carcinoma

Immunohistochemical Study of CD68, CD3 and Bcl-2 and their Role in Progression and Prognosis of Head and Neck Squamous Cell Carcinoma

Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases

DIDS inhibits overexpression BAK1‐induced mitochondrial apoptosis through GSK3β/β‐catenin signaling pathway

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