Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xeroderma pigmentosum group C (XPC) is an important DNA damage recognition protein that binds to damaged DNA at a very early stage during DNA repair. The XPC protein is also involved in DNA damage-induced cell cycle checkpoint regulation and apoptosis. XPC defects are associated with many types of solid tumors. The mechanism of the XPC protein in cancer progression, however, remains unclear. In this report, we showed the strong correlation between bladder cancer progression and attenuated XPC protein expression using tissues derived from patients with bladder cancer. The results obtained from our immunohistochemical studies further revealed a strong correlation of XPC deficiency, p53 mutation, and the degree of malignancy of bladder tumors. In addition, the results obtained from our studies have also shown that HT1197 bladder cancer cells, which carry a low-level XPC protein, exhibited a decreased DNA repair capability and were resistant to cisplatin treatment. When an XPC gene cDNA-expression vector was stably transfected into the HT1197 cells, however, the cisplatin treatment-induced apoptotic cell death was increased. Increased p53 and p73 responses following cisplatin treatment were also observed in HT1197 cells stably transfected with XPC cDNA. Taken together, these results suggest that XPC deficiency is an important contributing factor in bladder tumor progression and bladder cancer cell drug resistance.
 ...
PMID:Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer carcinogenesis and progression. 1751 Mar 83

Xeroderma pigmentosum group C (XPC) interacts with hHR23B to recognize DNA damage in global genomic repair. We previously showed that XPC is predominantly affected by its hypermethylation and is associated with an increased occurrence of p53 mutation in lung cancer. Tumors with low XPC mRNA levels had a poorer prognosis than those with high XPC mRNA levels, suggesting that XPC defects may enhance tumor metastasis. However, the underlying mechanism is unclear. Here, we show that p53 transcriptional activity is modulated by XPC, whereby XPC stabilizes hHR23B to form an hHR23B-p53 complex that prevents p53 degradation. In addition, in lung cancer cells and xenograft tumors in nude mice, overexpression of XPC suppresses cell/tumor metastatic ability via repression of matrix metalloproteinase-1 (MMP1) transcription by p53. Among tumors from lung cancer patients, those with low XPC mRNA also tended to have low expression of MMP1 mRNA compared with those with high XPC mRNA. Patients with low XPC mRNA levels also more commonly had tumors with late-stage, distant metastasis (M1), nodal metastasis, and T value (P < 0.001 for tumor stage, distant metastasis, and nodal metastasis; P = 0.006 for t value). In conclusion, p53 dysfunction caused by XPC defects in lung cancers may enhance tumor metastasis via increased MMP1 expression.
 ...
PMID:p53 dysfunction by xeroderma pigmentosum group C defects enhance lung adenocarcinoma metastasis via increased MMP1 expression. 2105 89