Growth Factor And Malignancy And Lkb1

AIM: To determine the effects of exogenous LKB1 gene on biological behavior of lung carcinoma cells. METHODS: Nest PCR was used to clone LKB1 gene pcDNA-LKB1 and pcDNA3.1 were introduced into A549 cell line by lipofectin transfection, and the A549 cells stably expressing LKB1 gene were established by G418 selection. The expression of LKB1 and STAT3 protein was detected by Western blot. Cell proliferation was observed by growth curve and clone formation. Cell cycle and apoptosis were assayed by flow cytometry(FCM)...

The tumor suppressor LKB1 (STK11) is a cytoplasmic/nuclear serine/threonine kinase, defects in which cause Peutz-Jeghers syndrome (PJS) in humans and animals. Recent studies showed that loss of function of LKB1 is associated with sporadic forms of lung, pancreatic, and ovarian cancer. In cancer cells, LKB1 is inactivated by two mechanisms: mutations in its central kinase domain or complete loss of LKB1 expression. Inactivation of LKB1 is associated with progression of PJS and transformation of benign polyps into malignant tumors...

Carcinogenesis is a dynamic and stepwise process, which is accompanied by a variety of somatic and epigenetic alterations in response to a changing microenvironment. Hypoxic conditions will select for cells that have adjusted their metabolic profile and can maintain proliferation by successfully competing for scarce nutritional and oxygen resources. In the present study we have investigated the effects of energy depletion in the context of HPV (human papillomavirus)-induced pathogenesis. We show that cervical carcinoma cell lines are susceptible to undergoing either growth arrest or cell death under conditions of metabolic stress induced by AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside), a known activator of the AMPK (AMP-activated protein kinase)...

AMPK is a serine/threonine protein kinase, which serves as an energy sensor in all eukaryotic cell types. Published studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumour cells. These actions of AMPK appear to be mediated through multiple mechanisms including regulation of the cell cycle and inhibition of protein synthesis, de novo fatty acid synthesis, specifically the generation of mevalonate as well as other products downstream of mevalonate in the cholesterol synthesis pathway...

The study of hereditary tumor syndromes has laid a solid foundation toward understanding the genetic basis of cancer. One of the latest examples comes from the study of tuberous sclerosis complex (TSC). As a member of the phakomatoses, TSC is characterized by the appearance of benign tumors, most notably in the central nervous system, kidney, heart, lung, and skin. While classically described as "hamartomas," the pathology of the lesions has features suggestive of abnormal cellular proliferation, size, differentiation, and migration...

PURPOSE: About one-third of sporadic lung adenocarcinomas demonstrates biallelic inactivation of the LKB1 gene, but the timing of this event is not known. DESIGN: We performed LKB1 immunohistochemistry on 35 primary lung adenocarcinomas and 96 atypical adenomatous hyperplasias (AAH), a form of early glandular neoplasia from which some lung adenocarcinomas arise. RESULTS: In all cases, strong cytoplasmic staining was noted in the non-neoplastic epithelium lining the airways from the bronchi to the terminal bronchioles...

UNLABELLED: Hamartomatous polyposis syndromes are characterized by an overgrowth of cells or tissues native to the area in which they normally occur. Juvenile polyposis syndrome (JPS) results from germ-line mutations in the SMAD-4 gene (18q21.1) that encodes for an enzyme involved in transforming growth factor beta(TGF-beta) signal transduction. The increased neoplastic risk may result from SMAD-4 mutations in the stromal component, which stimulate epithelial dysplasia and progression to invasive malignancy...