Dr. Langenfeld 's Lab Focuses On The Genes That Regulate Lung Cancer

What are lung cancers? Lung cancers are the abnormal cells which grow in uncontrolled manner in one or both lungs. They do not function as normal lung cells and do not develop into healthy lung tissue. The abnormal cells can grow, form tumours and interfere with the normal functions of the lung (Lungcancer.org, 2015). Lung cancers can be divided into two major types, namely non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC can be further classified into three main subtypes, namely adenocarcinoma, squamous-cell carcinoma and large-cell carcinoma (Longo & Harrison, 2012). Lung cancers can be diagnosed by chest X-ray, computerised tomography (CT) scan, positron emission tomography-computerised tomography (PET-CT) scan, bronchoscopy and biopsy (Nhs.uk, 2015). Unfortunately, lung cancers are often diagnosed at the later stages. This is due to the unrecognisable symptoms and warning signs at the earlier stages. NSCLC are often diagnosed at stage IV which accounts for 30-40% of cases whereas 60% of SCLC is diagnosed at stage IV. Lung cancer usually originates from the cells lining the bronchi, bronchioles and alveoli. Carcinogens especially tobacco smoke will alter the gene expression of the normal human lung cells, resulting in cell mutation. The proto-oncogenes will be converted to mutated form, oncogenes. Mutation leads to the decreased expression of the tumour suppressor genes. This results in uncontrolled cell proliferation, cell

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

Lung Cancer, like any other type of cancer, is the uncontrollable growth of cells in the lung tissue. The main causes that contribute to lung cancer include inhaling carcinogens (basically, smoking), exposure to ionizing radiation, viral infections and even air pollution. These factors basically damage the tissues lining the bronchi in the lung, leading the cancer to develop further (Vaporciyan & Nesbitt JC, 2000). Primary lung cancers that develop in the epithelial tissues of the lung are known as carcinomas and claim the top spot in terms of leading cancer-related death causes. As of 2004, lung cancer

Lung cancer is a cancer (malignancy) that originates in the tissues of the lungs or the cells lining the airways. Lung cancer originates when normal lung cells become cancer cells, usually after a series of mutations, and begin to divide out of control.

The purpose of this research was to determine the mechanisms in naked mole-rats that restricts cell proliferation and tumor formation. Contact inhibition is a mechanism observed where cell proliferation stops when two cells come in contact with one another. This process is caused by elevated levels of p27 cyclin-dependent kinase inhibitor which stops cells in the G1 phase from dividing. The cylcin-dependent kinase inhibitor p16 is also thought to regulate contact inhibition but its levels do not change in mice or human samples. Tumor-suppressor genes Rb and p53 are present in high concentration during contact inhibition to help control cell proliferation and apoptosis respectively. It was hypothesized that the naked mole-rats' cancer resistivity

In order to become cancerous a cell has many molecular changes that can occur including: tumor suppressor gene inactivation, oncogene activation, telomerase lengthening, ability to evade apoptosis, and angiogenesis (Mechanisms in Medicine, 2012). There are a few particular

Moore, S. W. (2009). Developmental genes and cancer in children. Pediatric. Blood Cancer, 52(7), 755-760. doi:10.1002/pbc.21831. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19165888

There are two important type of genes responsible for the development or cancer namely tumor suppressor because their normal function is

The cells continue proliferation within the bone marrow microenvironment, even in the presence of BMPs. Hence, it is essential to understand how tumor cells in bone marrow escape the effect of BMPs to continue growth. The main aim was to find how knockdown of BMPR2 influences BMPs and antagonist activin A.

TTF-1 ( Nkx2-1), a homeodomain-containing nuclear transcription factor has been a marker in the diagnosis of lung adenocarcinomas and in differentiating them from tumors of other origin.(1) Nkx2-1 is known for its transcriptional activity in the developing lung, thyroid and forebrain. Altered expression of TTF-1 resulting from mutations, polymorphisms and/or epigenetic modifications can predispose an individual to developmental disorders including thyroid dygenesis and thyroid cancer.(2) Mutations of the TTF-1 gene that induce haploinsufficiency may endow a negative effect on the wild-type gene.(3) Nkx2.1 is essentially involved with morphogenesis in the lung by modulating epithelial-mesenchymal interaction. Mouse models with functional

Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires a series of mutation during mitosis to develop, its characteristics can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells have make it hard to find a single effective treatment for cancer. The focus of research now lies

The murine double minute 2 (MDM2) gene is a protein that was first discovered in 1992.Researchers discovered that the gene was responsible for transforming a line of healthy rodent cells into cancerous cells [1]. Further studies revealed that artificially manipulating the MDM2 gene to produce more of its proteins in strains of mice with reduced immune system resulted in the development of tumors in the connective tissues of these mice. Cultured cells are transmuted due to the overexpression of MDM2 cells. This phenomenon also results in the immortalization of primary fibroblasts in rodents. The transformed mouse cell line 3T3-DM includes three genes, one of which is the MDM2. The genes were situated on small, acentromeric, extrachromosomal

The lung cancer cells especially in non-small cell lung cancer (NSCLC) are the primary target cells for this study. In addition to the lung cancer cells, the human breast cancer cells and pancreatic cancer cells are selected for the study in order to compare and confirm the similar activities of the gene expression and mechanism that induce these cancers.

Cells — Normal Human Bronchial Epithelial (NHBE) cells were obtained from Lonza (Walkersville, MD) and were grown and maintained in bronchial epithelial basal medium (BEGM, Lonza) supplemented with growth factors and hormones as described in the manufacturer's instructions, at 37°C in a humidified atmosphere of 5% CO2-95% air. Cells were treated with 15d-PGJ2 or Vehicle (Veh) in basal medium for 24 h, nuclear extracts were prepared and protein concentrations were determined using the BCA Protein Assay kit (Pierce, Rockford, IL).

The afore mentioned intricate network of interactions during EMT leads to many important changes in the phenotype and behavior of the cells. Epithelial cells undergo prominent morphological changes including the loss of cell-cell adhesion and the loss of apical-basal polarity. The cobblestone-like monolayer of epithelial cells with an apical-basal polarity is converted to dispersed, spindle-shaped mesenchymal cells with migratory protrusions. In addition to these morphological changes, cells undergoing EMT loose the expression of E-cadherin and other epithelial differentiation markers and gain the expression of mesenchymal markers such as vimentin, N-cadherin and fibronectin. These changes lead to the acquisition of migratory and invasive properties which enable the cells to migrate and invade through the ECM and the adjacent stroma (Boyer and Thiery, 1993). Thus, during cancer progression the EMT confers all the traits to the carcinoma cells which are required to overcome natural tissue barriers on their way to metastasis formation. These gained traits go hand in hand with a reduced proliferative potential of the mesenchymal-like tumor cells (Vega et al., 2004).