Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death.

GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized.

HOPX is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer.

HOPX acts as a tumour suppressor in various cancers. However, the regulation of HOPX in human lung cancer as well as the mechanism underlying its tumour-suppressive function has not yet been well elucidated. Here we investigated the epigenetic regulation and molecular mechanism by which HOPX exerts growth inhibitory effects.

The p53 target gene desmocollin 3 acts as a novel tumor suppressor through inhibiting EGFR/ERK pathway in human lung cancer.

Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Altered expression of desmocollin 3 (DSC3), a member of the desmosomal cadherin family, was found in various cancers; however, its functional involvement in carcinogenesis has not yet been elucidated. Expression/localization of DSC3 was analyzed by real-time reverse transcription-PCR, western blotting, immunofluorescence and immunohistochemistry.

Molecular cytogenetic characterization of epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor whose pathological diagnosis can be difficult. In the literature two cases of EHE were found to harbor a balanced t(1;3)(p36.3;q25) translocation, suggesting a characteristic chromosomal rearrangement as cause for the development of EHE.

The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression in human non-small cell lung cancer.

Objectives: The expression patterns of cytokeratin (CK) filaments in human epithelial neoplasms are complex and distinctive. The aims of this study were to analyze CK expression and to evaluate the diagnostic application of CKs in human non-small cell lung cancer (NSCLC).

Methods: mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19 was analyzed by Northern blotting.

Core classification of head and neck squamous cell carcinomas: correlations between morphology, DNA ploidy and HPV infection.

Aims: The study intended to reveal whether HPV infection is reflected by nuclear morphology and DNA cytometry parameters in head and neck squamous cell carcinomas (HNSCC).

Methods: In total, 39 HNSCC were selected for reanalysis by histomorphology applying the core classification, DNA cytometry and HPV detection. For the core classification, HE sections were assessed by a score system to evaluate the nuclear size, the mitosis size, their variabilities and the presence of tripolar or tetrapolar mitoses.

Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer.

DNA amplifications, leading to the overexpression of oncogenes, are a cardinal feature of lung cancer and directly contribute to its pathogenesis. To uncover such novel alterations, we performed an array-based comparative genomic hybridization survey of 128 non-small-cell lung cancer cell lines and tumors. Prominent among our findings, we identified recurrent high-level amplification at cytoband 22q11.

Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer.

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types.

Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer.

The homeobox containing gene HOP (Homeodomain Only Protein) was identified in the developing heart and lung where it functions downstream of Nkx2.5 and Nkx2.1 to modulate cardiac and lung gene expression.

Antigenicity testing by immunohistochemistry after tissue oxidation.

Aims: Archived tissue blocks preserve the antigenicity of samples for a long time under normal storage conditions, whereas tissue sections may show a diminished immunoreactivity over time. Little is known about the processes responsible for antigenicity loss and how tissue sections should be conserved for extended storage. Oxidation and drying are presumed mechanisms of antigenicity loss.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer.

The expression of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is decreased in various tumours, but the role of IGFBP-rP1 in lung cancer is not yet clear. In this study, IGFBP-rP1 expression in lung cancer cell lines was evaluated and reduced expression of IGFBP-rP1 was found. In tissue microarrays containing 138 primary tumours and 20 normal lung tissues analysed by immunohistochemistry, 58 tumours (42%) exhibited no expression of IGFBP-rP1, while all 20 normal lung tissues showed high expression.

5-Bromodeoxyuridine induced differentiation of a human small cell lung cancer cell line is associated with alteration of gene expression.

Small cell lung cancer (SCLC) appears to arise from neuroendocrine cells with the potential to differentiate into a variety of lung epithelial cell lineages. In order to investigate molecular events underlying the cell type transition in SCLC, we treated a SCLC cell line H526 with a differentiation inducing agent 5-bromodeoxyuridine (BrdU). The treatment led to a dramatic conversion from suspension cells to adherent cells exhibiting an epithelioid phenotype, which remarkably reduced the ability of colony formation in soft agar and suppressed the tumor growth rate in nude mice.

Decreased PITX1 homeobox gene expression in human lung cancer.

The PITX1 (pituitary homeobox 1) gene has essential roles in human development and has been considered a tumor suppressor in various cancers. However, in lung cancer the role of PITX1 remains to be elucidated. In this study, we analyzed the expression of PITX1 at both mRNA and protein levels in human lung cancer.

Decreased expression of insulin-like growth factor binding protein 7 in human colorectal carcinoma is related to DNA methylation.

Purpose: Insulin-like growth factor binding protein 7 (IGFBP-7) is considered a tumor suppressor in various cancers, but its role in colorectal cancer (CRC) is still uncertain. The aims of this study were to analyze the IGFBP-7 expression, and explore the mechanism responsible for the inactivation of IGFBP-7 in CRC.

Methods: mRNA expression was studied by RT-PCR and Northern blot analysis of cultured cells.

Chromosomal imbalances in wood dust-related adenocarcinomas of the inner nose and their associations with pathological parameters.

Comparative genomic hybridization (CGH) was used to screen 42 wood dust-related sinonasal adenocarcinomas for chromosomal alterations. The tumour collection comprised 39 papillary-tubular cylinder cell adenocarcinomas (PTCCs; six cases G1, 23 G2, and ten G3), two alveolar goblet cell adenocarcinomas (AGCs), and one signet ring cell adenocarcinoma (SRC), according to the Kleinsasser and Schroeder classification. Copy number changes were detected in 41 tumours (97.

Differentially expressed genes associated with human lung cancer.

To investigate the gene expression of 9 cDNA clones generated by suppression subtraction hybridization (SSH), Northern blot analysis was performed on a panel of immortalized bronchial epithelial cell lines, lung cancer cell lines and normal human bronchial epithelial cells (HBEC). The clones were located on chromosomes 1q, 2q, 3p, 3q, 4q and 14q representing regions that are frequently affected by DNA imbalances as shown by comparative genomic hybridization (CGH). Two were unknown (H24, H103) whereas the others matched to the Pest-containing nuclear protein (H52), Rp11-767C1 gene (H134), the hypothetical gene AK025444 (H238), Guanine nucleotide binding protein (G protein)/alpha inhibiting activity polypeptide 2 (H268), Laminin gamma 1 (Y45), the DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 9 (Y162) and the heat shock 90 kDa protein 1, alpha (Y238).

Characterization of {gamma}-aminobutyric acid type A receptor-associated protein, a novel tumor suppressor, showing reduced expression in breast cancer.

Frequent allelic loss of the chromosomal region 17p13 in breast cancer has suggested that more tumor suppressor genes, besides p53, are located in this region. By doing suppression subtractive hybridization to detect differentially expressed genes between the breast cancer cell line CAL51 and a nontumorigenic microcell hybrid CAL/17-1, we identified the gene for the gamma-aminobutyric acid type A (GABA(A)) receptor associated protein (GABARAP), located on 17p13.1.

[Study on relationship between p63 expression and 3q27-q29 alteration in non-small cell lung cancer].

Background: To investigate the relationship of p63 expression and p63 locus at chromosomal 3q27-q29 in non-small cell lung cancer (NSCLC).

Methods: Chromosomal imbalance in 30 cases of squamous cell carcinoma (SCC) and 40 cases of adenocarcinoma of the lung were evaluated by comparative genomic hybridization (CGH) technology. A tissue microarray of specimens from 122 primary NSCLC specimens was employed and used for immunohistochemical detection of p63 protein expression.

Downregulation of connexin 26 in human lung cancer is related to promoter methylation.

Cell-Cell communication via gap junctions plays a key role in carcinogenesis and in growth control. One of the gap junction proteins, Connexin 26 (Cx26) was considered as tumor suppressor in various cancers. In our study, the expression of Cx26 was analyzed in human lung cancer.

[Evaluation of p63 expression in lung cancer by use of complementary DNA and tissue microarray].

Objective: To study p63 expression at mRNA transcript and protein levels in human lung cancers, including squamous cell lung carcinoma (SCC), adenocarcinoma, large cell lung carcinoma (LCLC) and small cell lung carcinoma (SCLC), or the corresponding metastatic foci. The relationship of p63 expression and alterations in p63 locus at chromosomal 3q27-29 was also determined.

Methods: p63 gene expression in 72 cases of SCC, adenocarcinoma, LCLC and SCLC was analyzed by cDNA microarray technology.

CGH pattern of esthesioneuroblastoma and their metastases.

Comparative genomic hybridization (CGH) was used to screen 22 esthesioneuroblastomas (ENB) from 12 patients including 12 primary tumors and 10 metastasis/recurrent lesions for chromosomal imbalances being the most extensive study so far. The analysis revealed a characteristic pattern consisting of deletions on chromosomes 3p and overrepresentations on 17q in up to 100% of cases. Other important alterations being detectable in more than 80% of cases were deletions on 1p, 3p/q, 9p, 10p/q along with overrepresentation on 17p13, 20p and 22q.

Analysis of the RNA helicase A gene in human lung cancer.

In this study we investigated the RNA helicase A (RHA) gene localized on chromosome 1q25 in 15 lung cancer cell lines, 54 primary carcinomas, bronchial epithelial cells and normal lung. Both RT-PCR and real-time RT-PCR showed that RHA is over-expressed in tumour samples compared to normal lung tissues (p=0.01).

Gene expression profiles in human non-small and small-cell lung cancers.

Suppression subtractive hybridisation (SSH) was performed comparing normal bronchial epithelial cells with a lung squamous cell carcinoma (SCC) and a metastatic small-cell lung carcinoma (SCLC). The sequence analysis of four cDNA libraries revealed 869 individual sequences. Of these, 342 were tested using northern blots of lung cancer cell lines representing the three major subtypes (SCC, adenocarcinoma, SCLC) which confirmed the differential expression of 236 cDNAs.

Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer.

We have isolated a novel gene, lung cancer-associated gene Y (LAGY), by suppression subtractive hybridization. The nucleotide sequence of LAGY predicts a small protein of 73 amino acids containing a putative homeobox domain with a molecular mass of 8.1 kD.

Identification of differentially expressed genes in immortalized human bronchial epithelial cell line as a model for in vitro study of lung carcinogenesis.

Suppression subtractive hybridization (SSH) was applied to identify differentially expressed genes in the SV40LT immortalized human bronchial epithelial cell line Y-BE, with normal human bronchial epithelial cells (HBEC) as a control. Two cDNA libraries of up- and downregulated genes were generated, comprising 218 known genes and 131 unknown genes in total. The expression of 22 clones from the 2 libraries was investigated by Northern blot analysis, and 86.