Immunohistochemical study of Skp2 and Jab1, two key molecules in the degradation of P27, in lung adenocarcinoma

Immunohistochemical study of Skp2 and Jab1, two key molecules in the degradation of P27, in lung adenocarcinoma
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DOI:
10.1111/j.1440-1827.2004.01679.x
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发表时间:
2004-09-01
影响因子:
2.2
通讯作者:
Fukayama, M
Fukayama, M
中科院分区:
医学4区
文献类型:
--
作者:
Goto, A;Niki, T;Fukayama, M

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为了阐明P27降解途径蛋白Skp2和Jab1与肺腺癌(AD)发生发展的关系,我们通过免疫组织化学方法研究了110例肺腺癌和11例非典型腺瘤性增生(AAH)中Skp2和Jab1的表达以及P27-和ki -67的标记,并分析了这些蛋白的表达与临床病理因素的关系。Skp2或Jab1高表达在肺AD中较为常见(分别为52/110、47%和59/110、54%),Jab1高表达在AAH中也较为常见(4/11、36%),而在正常细支气管上皮中未见。P27标记指数(LI)与Skp2和Jab1高表达呈负相关,Ki-67 LI高表达与Skp2和Jab1高表达显著相关。然而,低P27表达与高Ki-67 LI无关。高Skp2肺AD与血液和淋巴管侵袭有显著相关性,而低P27表达与肺AD无相关性。此外,Skp2在肺AD中的高表达与患者的不良预后显著相关。因此,Skp2和Jab1调节P27的降解,并可能通过P27介导和非P27介导的机制参与肺AD的发生和进展。
To clarify the association of the P27 degradation pathway proteins, Skp2 and Jab1, with the development and progression of lung adenocarcinoma (AD), we immunohistochemically investigated Skp2 and Jab1 expression together with P27- and Ki-67-labeling in 110 lung AD and 11 atypical adenomatous hyperplasia (AAH) and analyzed the relationship between the expression of these proteins and the clinicopathological factors. High Skp2 or Jab1 expression was frequent in lung AD (52/110, 47%, and 59/110, 54%, respectively), and high expression of Jab1 was also frequent in AAH (4/11, 36%), while it was not observed in normal bronchiolar epithelium. The P27 labeling index (LI) was reciprocally correlated with high Skp2 and Jab1 expression, and a higher Ki-67 LI was significantly correlated with high Skp2 and Jab1 expression. However, low P27 expression did not correlate with a higher Ki-67 LI. High Skp2 lung AD showed significant correlation with blood and lymphatic vessel invasion, which low P27 expression did not correlate with. Furthermore, high Skp2 expression in lung AD was significantly correlated with a poor outcome for patients. Thus, Skp2 and Jab1 regulate P27 degradation, and might contribute to the development and progression of lung AD through P27-mediated and -unmediated mechanisms.