Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck

Pena, John C.; Thompson, Craig B.; Recant, Wendy; Vokes, Everett E.; Rudin, Charles M.

doi:10.1002/(sici)1097-0142(19990101)85:1<164::aid-cncr23>3.0.co;2-q

Cited by 124 publications

(93 citation statements)

References 42 publications

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“…Further studies with these mice demonstrated that they developed more papillomas than control mice and that Bcl-x L overexpression can dramatically increase the malignant conversion rate of benign tumors (Pena et al, 1998). These studies suggest that inappropriate expression of Bcl-2 family members can promote tumorigenesis and provide evidence that the apoptotic pathway is an important mechanism in maintaining normal tissue homeostasis in the skin.…”

Section: Introductionsupporting

confidence: 91%

“…The expression of these proteins in skin suggests that they may have a fundamental role in protecting keratinocytes from cell death induced by UV radiation and other mutagens. The role of Bcl-2 and Bcl-x L in skin development, di erentiation and apoptosis has been analysed by generating transgenic mice that overexpress these proteins in the epidermis (RodriguezVillanueva et al, 1998;Pena et al, 1997Pena et al, , 1998. The skin from mice expressing a keratin-1 driven Bcl-2 transgene exhibited increased proliferation and the keratinocytes from these mice were signi®cantly more resistant to cell death induction by UV radiation, DMBA and TPA (Rodriguez-Villanueva et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

et al. 1999

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The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bclx L is a well-described cell survival protein that when overexpressed in skin can protect keratinocytes from UV radiation-induced apoptosis. To begin to unravel the complex mechanisms that keratinocytes use to survive, we wanted to characterize the role of endogenous Bcl-x L in protecting cells from death. In this study, we describe the development and characterization of an antisense inhibitor to Bcl-x L . We show that this inhibitor reduces Bcl-x L RNA and protein in a concentration-dependent, sequence-speci®c manner. Furthermore, treatment of keratinocytes and epithelial cells with this inhibitor sensitizes these cells to UV-B radiation and cisplatinum treatment-induced apoptosis. Thus, these results o er direct evidence that Bcl-x L is critical in the protection of skin and epithelial cells from apoptosis and provide a basis for the role of Bcl-x L in keratinocyte and epithelial cell survival.

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Section: Introductionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

et al. 1999

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“…59 Bcl-x overexpression was associated with unfavorable clinical outcome in invasive breast cancer 41 and prostatic adenocarcinoma, 60 but not associated with clinical outcome in head and neck SCC. 38 Fas expression is also reported not to be associated with prognosis in laryngeal carcinoma. 13 Therefore, prognostic values of apoptosis-related proteins may vary between tumor sites and/or types, but it is likely, on the basis of previous reports 6,37,39 and the current data, that the overexpression of bax may be predictive of a favorable clinical outcome in head and neck SCC, including maxillary sinus SCC.…”

Section: Discussionmentioning

confidence: 95%

“…13 The expression of bax and bcl-x was categorized as follows: negative if no staining was seen in tumor cells or if only a weak positive and heterogeneous staining was observed in less than 30% of tumor cells, and positive if staining was observed in more than 30% of tumor cells, according to reports. 38,45 More than 5000 tumor cells were counted to calculate the apoptotic index (AI) in at least five high power fields, and the AI values were defined as the number of ss DNA positive cells per 1000 tumor cells. 39,40 Sections with anti-mouse immunoglobulin G1 monoclonal antibody were used as negative controls.…”

Section: Immunohistologic Analysesmentioning

confidence: 99%

“…19 Overexpression of bcl-x has been reported to protect tumor cells from apoptosis, 32 whereas increased bax expression promotes apoptosis induced by cytotoxic drugs and radiation. 33,34 Expression of apoptosisrelated proteins such as bax, [35][36][37] bcl-x, 38 Fas, 13 and spontaneous apoptosis 39 has been analyzed immunohistologically in head and neck SCC. However, the results have not been uniform with regard to the correlation between their expression and prognosis.…”

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confidence: 99%

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Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

Bandoh

Hayashi

Kishibe

et al. 2002

Cancer

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Molecular Profiling and the Identification of Genes Associated With Metastatic Oral Cavity/Pharynx Squamous Cell Carcinoma

Schmalbach

Chepeha

Giordano

et al. 2004

Arch Otolaryngol Head Neck Surg

104

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Objective: To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors.Design: Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin.Subjects: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy.Results: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change Ն1.5; PϽ.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change Ն1.5; PϽ.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 ␣-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P =.003). Conclusions:Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.

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Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck

Cited by 124 publications

References 42 publications

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

Molecular Profiling and the Identification of Genes Associated With Metastatic Oral Cavity/Pharynx Squamous Cell Carcinoma

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