Quantitative expression analysis of the apoptosis-related gene, BCL2L12, in head and neck squamous cell carcinoma.

Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece First Ear, Nose and Throat Clinics, Faculty of Medicine, University of Athens, Athens General Hospital 'Hippokration', Athens, Greece.
Journal of Oral Pathology and Medicine (Impact Factor: 2.06). 07/2012; DOI: 10.1111/j.1600-0714.2012.01190.x
Source: PubMed

ABSTRACT J Oral Pathol Med (2012) Background:  BCL2L12 is a recently identified gene belonging to the BCL2 family, members of which are implicated in head and neck squamous cell carcinoma (HNSCC). We have recently shown that BCL2L12 mRNA expression is an unfavorable prognostic indicator in nasopharyngeal carcinoma (NPC) and that BCL2L12 can be regarded as a novel, useful tissue biomarker for the prediction of NPC patients' short-term relapse. The aim of this study was to analyze the mRNA expression of the novel apoptosis-related gene BCL2L12 in patients with HNSCC. Methods:  Total RNA was isolated from 53 malignant tumors originating in larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissue specimens, resected from patients with HNSCC. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification in head and neck tissues was developed using the SYBR(®) Green chemistry. After preparing cDNA by reverse transcription, relative quantification was performed using the comparative C(T) () method. Results:  BCL2L12 mRNA levels were lower in laryngeal tumors of advanced tumor, node, metastasis (TNM) stage or bigger size and in well-differentiated malignant tongue neoplasms, compared with early-stage laryngeal tumors or poorly differentiated tongue tumors. Interestingly, the BCL2L12 expression showed significant discriminatory value, distinguishing efficiently patients with tongue squamous cell carcinoma (SCC) from non-cancerous population. Conclusions:  This is the first study examining the BCL2L12 mRNA expression in HNSCC. Our results suggest that BCL2L12 mRNA expression may serve as a potential prognostic biomarker in tongue and/or larynx SCC, which principally constitute the great majority of HNSCC cases worldwide.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor of the central nervous system (CNS). As an attempt to identify drugs for GBM therapeutics, phenotypic assays were used to screen 3000 chemicals from a clinical compound library. GBM subtypes exhibited different capabilities to induce angiogenesis when cultured on Matrigel; proneural cells migrated and formed a tube-like structure without endothelial cells. Among the compounds screened, indatraline, a nonselective monoamine transporter inhibitor, suppressed these morphological changes; it dose dependently inhibited cell spreading, migration, and in vitro/in vivo tube formation. In addition to intracellular calcium concentration, indatraline increased the level of Rho GTPase and its activity. Moreover, indatraline downregulated angiogenesis-related genes such as IGFBP2, PTN, VEGFA, PDGFRA, and VEGFR as well as nestin, a stem cell marker. These findings collectively suggest that the activation of Rho GTPase and the suppression of angiogenesis-related factors mediate the antiangiogenic activity of indatraline in proneural GBM culture.
    Biochemical and Biophysical Research Communications 12/2013; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Colorectal cancer (CRC) is one of the three most common cancers in both genders. Even though several biomarkers are in use in diagnosis and prognosis of the disease, they are marred by limited specificity and sensitivity. The human kallikrein-related peptidase 10 (KLK10) gene is a member of the human tissue kallikrein family. Because prostate specific antigen (PSA), the best biomarker for detecting and monitoring prostate cancer, is a member of this family, many other members, including KLK10, have been widely examined as novel biomarkers for different cancer types. In previous studies, KLK10 has been proposed as a diagnostic biomarker for ovarian carcinoma, while its methylation on exon 3 has been proposed as a prognostic marker for early-stage breast cancer patients. The purpose of this study was to analyse KLK10 mRNA expression and examine its prognostic value and potential clinical application as a novel molecular tissue biomarker in CRC. Design and methods The study group consisted of 190 colorectal samples. Total RNA was extracted from pulverised tissues and cDNA was prepared by reverse transcription. KLK10 was amplified by real-time PCR. B2M was used as a reference gene and HT-29 cells as positive control. RESULTS: KLK10 expression was significantly higher in cancer tissues (P<0.001). Tumours of advanced TNM and Duke's stage showed high KLK10 expression status (P=0.036; P=0.025). Patients with high KLK10 expression had a shorter disease-free and overall survival rates (P=0.014; P=0.020). CONCLUSIONS: Our results suggest that KLK10 may serve as a new marker of unfavourable prognosis of colorectal cancer.
    Clinical biochemistry 03/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma progression is mainly characterized by intense apoptosis resistance and marked necrosis. Over-expression of BCL2L12, a novel member of Bcl-2 family has been shown in primary glioblastoma. BCL2L12 blocks effective caspase-3/7 maturation and inhibits p53 tumor suppressor, deriving resistance toward apoptosis and inducing extensive cell necrosis. Cisplatin is a major chemotherapeutic agent which has a broad range of anti-neoplastic activities including apoptosis induction. To investigate the effect of cisplatin on the expression of BCL2L12 in glioblastoma cells, two glioblastoma cell lines were treated with different concentrations of cisplatin for 48 h. The cell viability and IC50 was determined using MTT assay. Then, the two glioblastoma cell lines were treated with 48 h IC50 concentration of cisplatin for 24, 48, and 72 h. Apoptosis induction was analyzed by fluorescence microscopy and flow cytometry. Gene expression study was performed on BCL2L12 and TBP as target and internal control genes, respectively. The quantitative real-time polymerase chain reaction results showed that BCL2L12 gene expression was significantly (p = 0.001) downregulated in the presence of cisplatin. In conclusion, cisplatin treatment induced a time-dependent apoptosis in glioblastoma cells, at least partially via downregulation of BCL2L12 gene expression.
    In Vitro Cellular & Developmental Biology - Animal 05/2013; · 1.29 Impact Factor


Available from
Jun 2, 2014