Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL-6) and leukaemia inhibitory factor (LIF) can have pleiotropic effects on different cell types. M1 myeloid leukaemic cells respond to IL-6 with activation of a terminal differentiation programme which includes activation of genes for certain haemopoietic regulatory proteins (IL-6, IL-1 alpha, IL-1 beta, granulocyte-macrophage colony-stimulating factor [GM-CSF], M-CSF, tumour necrosis factor and transforming growth factor [TGF] beta 1) and for receptors for some of these proteins, thus establishing a network of positive and negative regulatory cytokines. IL-6 and some other cytokines also induce during differentiation sustained levels of transcription factors that can regulate and maintain gene expression in the differentiation programme. M1 leukaemic cells induced to differentiate with IL-6 undergo programmed cell death (apoptosis) on withdrawal of IL-6, and can be rescued from apoptosis by IL-6, IL-3, M-CSF, G-CSF or IL-1, but not by GM-CSF. These differentiating leukaemic cells can also be rescued from apoptosis by the tumour promoter TPA (12-O-tetradecanoylphorbol-13-acetate) but not by the non-tumour-promoting isomer 4-alpha-TPA, and rescue from apoptosis can be achieved by different pathways. Apoptosis can also be induced in undifferentiated M1 leukaemic cells by expression of the wild-type form of the tumour suppressor p53 protein and IL-6 can rescue the cells from this wild-type p53-mediated apoptosis. There are clones of M1 cells that differentiate with IL-6 but not with LIF and another M1 clone that differentiates with either IL-6 or LIF. Differentiation induced by IL-6 or LIF is inhibited by TGF-beta 1. The pleiotropic effects of LIF, like those of IL-6, are presumably also in a network of interacting regulatory proteins.
 ...
PMID:Regulation of leukaemic cells by interleukin 6 and leukaemia inhibitory factor. 142 20

Using the thyroid follicular cell as a model for multi-stage carcinogenesis, we have investigated the role of two potential negative growth regulators ('anti-oncogenes') in epithelial tumour progression--transforming growth factor-beta 1 (TGF beta 1) and p53. Normal follicular cells, as expected, showed marked growth inhibition in response to TGF beta 1. Adenoma cells were equally inhibited. In contrast, spontaneously and SV40-immortalised follicular cell lines showing features of malignant transformation (notably loss of growth factor dependence) had lost all responsiveness to TGF beta 1, accompanied by a partial loss of its receptors. p53 protein was below detectable limits in normal and in adenoma cells but in contrast very high levels were observed in all three transformed lines. In the SV40-immortalised cells, this was expected in view of the known stabilising effect of the viral large T protein. In the spontaneous line we found strong evidence for point mutation of p53, which is known to have the same effect. Both mechanisms result in loss of p53 tumour suppressor function despite increased protein content. We conclude that loss of inhibition by TGF beta and inactivation of p53 are important steps in in vitro immortalisation and/or in vivo tumour progression in human thyroid follicular cells, and speculate that p53 may mediate or be required for the inhibitory signal normally induced by TGF beta 1.
 ...
PMID:Correlated abnormalities of transforming growth factor-beta 1 response and p53 expression in thyroid epithelial cell transformation. 182 Sep 69

Malignant cells usually show altered gap junctional intercellular communication and are often associated with aberrant expression or localization of connexins. Transfection of connexin genes into tumorigenic cells restores normal cell growth, suggesting that connexins form a family of tumour suppressor genes. Some studies have also shown that specific connexins may be necessary to control growth of specific cell types. Although we have found that genes encoding connexin32 (Cx32; beta 1), Cx37 (alpha 4) and Cx43 (alpha 1) are rarely mutated in tumours, our recent studies suggest that methylation of the connexin gene promoter may be a mechanism by which connexin gene expression is down-regulated in certain tumors. We have produced various dominant negative mutants of the genes encoding Cx26 (beta 2), Cx32 and Cx43, some of which prevent the growth control exerted by the corresponding wild-type genes. A decade ago, we proposed a method to enhance killing of cancer cells by diffusion of therapeutic agents through gap junctions. Recently, we and others have shown that gap junctional intercellular communication is responsible for the bystander effect seen in herpes simplex virus thymidine kinase/ganciclovir gene therapy. Thus, connexin genes can exert dual effects in tumour control: tumour suppression and a bystander effect for cancer therapy.
 ...
PMID:Connexins in tumour suppression and cancer therapy. 1020 8

Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.
 ...
PMID:Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective. 1066 Apr 90

Given the low resection rate and chemoresistance of patients with pancreatic cancer (PC), their survival rates are typically poor. Long noncoding RNAs (lncRNAs) have recently been shown to play an important role in tumourigenesis and human cancer progression, including in PC. In this study, we aimed to investigate the role of taurine-upregulated gene 1 (TUG1) in PC. A quantitative polymerase chain reaction was used to analyse TUG1 expression in PC tissues and peritumoural normal tissues. TUG1 was overexpressed in PC tissues compared with that in peritumoural normal tissues, and the high expression of TUG1 was associated with the poor prognosis of patients with PC. Furthermore, TUG1 knockdown significantly inhibited the proliferation and invasion of PC cells both in vitro and in vivo, while overexpression TUG1 promoted tumour cell proliferation, migration, and invasion. TUG1 directly targeted miR-29c, a tumour suppressor in several cancers. TUG1 knockdown significantly increased the expression of miR-29c and subsequently induced the downregulation of integrin subunit beta 1 (ITGB1), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The downregulation of miR-29c abolished the TUG1 knockdown-mediated inhibition of tumour growth in vitro and in vivo, whereas the upregulation of miR-29c enhanced the effects of TUG1 knockdown on PC cells. In conclusion, we demonstrate for the first time the oncogenic role of TUG1 in PC. The downregulation of TUG1 significantly inhibited the growth and migratory ability of PC cells in vitro and in vivo by targeting miR-29c. Our study provides a novel potential diagnostic biomarker and therapeutic target for PC.
 ...
PMID:Long Noncoding RNA TUG1/miR-29c Axis Affects Cell Proliferation, Invasion, and Migration in Human Pancreatic Cancer. 3059 64