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The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells

Nasopharyngeal carcinoma (NPC) occurs occasionally in the west but is popular in south-eastern China and Hong Kong where it is the third most common form of malignancy among ethnic Chinese people. The possibly relevant factors associated with NPC have been found, for example, environment, genetics and EB virus, etc. Recently, as a result of improved environment of living and therapies, the death rate of NPC is decreasing year by year. However, the molecules mechanism underlying its tumorigenicity is still unclear.
The p57 protein is a maternally expressed, paternally imprinted cyclin-dependent kinases inhibitor (CDI). p57 mutations are rare in the human cancers, suggesting that other mechanisms of transcriptional or post translational silencing are involved in the loss of p57 function. Decreased expression of p57 has been found in Beckwith-Wiedemann syndrome (BWS), gastric cancer and bladder carcinoma. So far, many studies in signal transduction have been focused on p21 or p27. The relationship between p57 expression and signal transduction and cell proliferation under physiological circumstances requires further exploration.
Studies of the relationship between hormones and cancers have been proceeded for years, nevertheless, there is few about NPC. We examined several hormones¡¦ effect on the NPC cell lines. We found that in response to progesterone treatment were the marked inhibition of pMAPK and up-regulation of p57, just like the influence of MEK inhibitor, U0126. Progesterone also induced growth inhibition and a slight accumulation of cells in the G1 phase of the cell cycle. On the other hand, the effects of progesterone were diminished in the presence of its antagonist mifepristone (RU-486). Taken together, these results suggest that progesterone treatment may induce the expression of the p57 on the mRNA and protein level by the progesterone receptor and that the MAPK signaling pathway may be involved in the progesterone-induced antiproliferative effect.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0914104-101456
Date14 September 2004
CreatorsHsu, Cheng-yuan
ContributorsPei-jung Lu, Hung-sheng Hsiao, Chung-lung Cho, Hong-yu Kang
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456
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