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)

Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses.
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PMID:Role of steroid hormones and growth factors in breast cancer. 1247 34

Retinoic acid (RA) and its natural and synthetic derivatives (retinoids) are important dietary factors which regulate cellular differentiation and growth, so that they are thought to be particularly effective at preventing the development of several tumours. They play this role as ligands of the RAR and RXR nuclear retinoic acid receptors, including the RA receptor isoforms alpha, beta, and gamma. These ligand-activated nuclear receptors induce the transcription of target genes by binding to RA-responsive elements in the promoter regions. Among these target genes, the RARbeta gene is of great interest, being able to encode a potential tumour suppressor. It should be emphasized that most breast carcinomas and breast cancer cell lines show loss or down-regulation of RARbeta receptor expression, whereas RARalpha and gamma, as well as retinoid X receptors, appear to be variably expressed in both normal and tumour cells. It is also interesting to note that basal and RA-induced RARbeta mRNA levels tend to increase with senescence of normal cells. This information provides further support for the hypothesis that genetic events involved in cellular senescence may also play a significant role in tumour suppression in humans. The aim of this review is to clarify whether expression of RARbeta could be modulated by chemopreventive intervention and may therefore serve as an intermediate biomarker in chemoprevention trials for some cancers.
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PMID:Nuclear retinoic acid receptor beta as a tool in chemoprevention trials. 1716 22

Lung cancer is the most common cancer-related death worldwide. Natural compounds have shown high biological and pharmaceutical relevance as anticancer agents. Retinoids are natural derivatives of vitamin A having many regulatory functions in the human body, including vision, cellular proliferation and differentiation, and activation of tumour suppressor genes. Retinoic acid (RA) is a highly active retinoid isoform with promising anti-lung cancer activity. The abnormal expression of retinoid receptors is associated with loss of anticancer activities and acquired resistance to RA in lung cancer. The preclinical promise has not translated to the general clinical utility of retinoids for lung cancer patients, especially those with a history of smoking. Newer retinoid nano-formulations and the combinatorial use of retinoids has been associated with lower toxicity and more favorably efficacy in both the preclinical and clinical settings. Here, we highlight epidemiological and clinical therapeutic studies involving retinoids and lung cancer. We also discuss the biological actions of retinoids in lung cancer, which include effects on cancer stem cell differentiation, angiogenesis, metastasis, and proliferative. We suggest that the use of retinoids in combination with conventional and targeted anticancer agents will broaden the utility of these potent anticancer compounds in the lung cancer clinic.
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PMID:The potential of retinoids for combination therapy of lung cancer: Updates and future directions. 3125 65