Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of multidrug resistance (MDR) proteins in tumour cells is associated with an increased resistance to therapy and in consequence with a decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) transporters. Neuroblastoma (NBL) and rhabdomyosarcoma (RMS) are common solid tumours of childhood. The response to therapy is better in NBL, worse in RMS, but still unsatisfactory despite surgery and aggressive chemotherapy. The immunohistochemical staining for p-gp (p-glycoprotein), MRP1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) expression was performed in primary tumour sections of NBL (10 cases) and RMS (10 cases). A different pattern of MDR expression in NBL and RMS were noted. In NBL, MRP1 was expressed in all studied tumours, p-gp, BCRP only in 3 out of 10 tumours, LRP, in 4 cases. The combination of more than one protein was noted in the majority of NBL tumours. In RMS, the expression of 3 or 4 MDR proteins was noted in 9 cases. The high expression of an MDR protein profile in RMS suggests various mechanisms acting simultaneously, which might explain chemotherapy resistance and a low percentage of long-time survival in this tumour.
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PMID:Expression of proteins associated with therapy resistance in rhabdomyosarcoma and neuroblastoma tumour cells. 2007 50

Neuroblastoma is the most common cancer of infancy and accounts for 15% of all pediatric oncology deaths. Survival rates of high-risk neuroblastoma remain less than 50%, with amplification of the MYCN oncogene the most important aberration associated with poor outcome. Direct transcriptional targets of MYCN include a number of ATP-binding cassette (ABC) transporters, of which ABCC1 (MRP1), ABCC3 (MRP3), and ABCC4 (MRP4) are the best characterized. These three transporter genes have been shown to be strongly prognostic of neuroblastoma outcome in primary untreated neuroblastoma. In addition to their ability to efflux a number of chemotherapeutic drugs, evidence suggests that these transporters also contribute to neuroblastoma outcome independent of any role in cytotoxic drug efflux. Endogenous substrates of ABCC1 and ABCC4 that may be potential candidates affecting neuroblastoma biology include molecules such as prostaglandins and leukotrienes. These bioactive lipid mediators have the ability to influence biological processes contributing to cancer initiation and progression, such as angiogenesis, cell signaling, inflammation, proliferation, and migration and invasion. ABCC1 and ABCC4 are thus potential targets for therapeutic suppression in high-risk neuroblastoma, and recently developed small-molecule inhibitors may be an effective strategy in treating aggressive forms of this cancer, as well as other cancers that express high levels of these transporters.
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PMID:ABC transporters and neuroblastoma. 2564 Feb 69