Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of melanoma antigen A (MAGE-A) genes are commonly detected in non-small cell lung cancers. Their biological function is not well characterized but may involve the regulation of apoptosis and cell cycle progression. We hypothesized that MAGE-A4 is involved in the regulation of apoptosis. To investigate this, expression of MAGE-A was evaluated. MAGE-A4 was expressed in 48% of non-small cell lung carcinomas. Ninety percent of lung carcinomas expressing MAGE-A4 were classified as squamous cell carcinomas and 10% were adenocarcinomas. Tumor-free surrounding lung tissue was negative for MAGE-A4. A molecular clone of MAGE-A4 derived from human lung cancer was stably expressed in human embryonic kidney cells (293 cells) to evaluate effects on cell death. Overexpression of MAGE-A4 increased apoptosis as measured by the apoptotic index (P < 0.0001) and caspase-3 activity (P < 0.002). Exposure to 25 micromol/L etoposide, a chemotherapeutic agent, increased the apoptotic effect (P < 0.0001). Furthermore, we show that MAGE-A4 silencing using a small interfering RNA approach results in decreased caspase-3 activity in the squamous cell lung cancer cell line H1703 by 58% (P = 0.0027) and by 24% (P = 0.028) in 293/MAGE-A4 cells. These findings suggest that MAGE-A4 expression may promote tumor cell death, sensitize malignancies to apoptotic stimuli, such as chemotherapeutic agents, and therefore may represent a tumor suppressor protein.
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PMID:Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis. 1665 21

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. In squamous cell lung cancer, low expression of IGFBP-rP1 was significantly linked to high-grade tumours. Treatment with 5-aza-2'-deoxycytidine restored the expression of IGFBP-rP1 in three of four lung cancer cell lines. Sequencing of PCR products of sodium bisulphite-treated genomic DNA from the three lung cancer cell lines revealed a heterogeneous methylation pattern in the region of exon 1 and intron 1. Stable transfection of IGFBP-rP1 full-length cDNA into the H2170 lung cancer cell line led to increased expression of IGFBP-rP1 protein. IGFBP-rP1-positive transfectants exhibited remarkably reduced colony-forming ability in soft agar, suppression of tumour growth rate in nude mice, and increased apoptotic cell number as well as activated caspase-3 expression level. The data suggest that IGFBP-rP1 is a tumour suppressor inactivated by DNA methylation in human lung cancer.
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PMID:Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer. 1723 81