RESUMEN
Non-small cell lung cancer is associated with approximately 85% mortality due to its high metastatic potential. Therapeutic efforts have failed to produce a significant improvement in prognosis. In this situation, a better understanding of the key factors of metastasis may be useful for designing new molecular targets of therapy. In order to identify these factors, we compared the expression profiles of two subpopulations of an adenocarcinoma cell line with a high metastatic potential, PC9/f9 and PC9/f14, with the parent cell line, PC9, using a cDNA array. The expression of 15 genes was found to be significantly enhanced or reduced in the highly metastatic subpopulations. The expression of matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor-1 (PAI-1) and interleukin-1 (IL-1 alpha) were upregulated in the highly metastatic subpopulations, while the expression of carcinoembryonic antigen (CEA), caspase-5, Fas ligand, Prk/FNK, cyclin E, cyclin B1, Ki-67, proliferating cell nuclear antigen (PCNA), Smad4, macrophage proinflammatory human chemokine-3 alpha (MIP-3 alpha)/LARC, Met and CD44 were downregulated. Data from the literature suggest that the altered expression of MMP-2, PAI-1, IL-1 alpha, CEA, caspase-5, Fas ligand, Prk/FNK and Smad4 promotes the highly metastatic phenotype. The differential expression of these genes was confirmed by Northern blot analysis, standard reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. This analysis in subpopulations of a lung cancer cell line indicated that the highly metastatic potential of lung cancer may be induced not by an alteration in the expression of a single gene, but by the accumulation of alterations in the expression of several genes involved in extracellular matrix (ECM) adhesion disruption, ECM degradation, escape from apoptosis, and resistance to transforming growth factor-beta(1) (TGF-beta(1)). Strategies for inhibiting metastasis of pulmonary adenocarcinoma should be designed accordingly.
Asunto(s)
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Oncogenes/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Animales , Northern Blotting , Regulación hacia Abajo , Matriz Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
The presence and quantity of protein A in Staphylococcus aureus 147 isolates from the tonsils of healthy pigs were examined by three methods. Cell-bound protein A was detected in 71 (48%), 104 (71%) and 123 (84%) of 147 isolates by the slide hemagglutination test, microplate hemagglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Extracellular protein A was not detected in any isolates by the microplate hemagglutination test. When the quantity of cell-bound protein A in the isolates was determined by the ELISA, most of the isolates contained about 0.8 to 2.2 micrograms of protein A/ml in bacterial cell suspensions of a concentration of MacFarland No. 3.