Differential regulation of p27Kip1 depending on culture conditions and its correlation with status of p14ARF and p53
Differential regulation of p27Kip1 depending on culture conditions and its correlation with status of p14ARF and p53
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DOI：
10.1111/gtc.12919
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发表时间：
2022-01-17
期刊：
影响因子：
2.1
通讯作者：
Chibazakura，Taku
中科院分区：
文献类型：
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作者：
Kometani，Tatsuya;Kawasaki，Yutaro;Chibazakura，Taku
p27 Kip 1是一种主要的细胞周期蛋白依赖性激酶抑制剂和肿瘤抑制剂，通常在蛋白水平上功能受阻。p27蛋白表达水平在各种癌症中经常是低的，并且与癌症的恶性程度负相关。然而，在我们以前的研究中，我们发现p27过表达并不能抑制两种癌细胞系的增殖，这是由于核磷蛋白亚型1（NPM 1）对p27的功能性抑制;也就是说，在这些癌细胞系中发生了对p27功能的定性而非定量抑制。为了阐明p27在几种类型癌症中的调控，我们研究了p27在其他癌细胞系中的功能，基于对携带多西环素诱导型p27的细胞系的增殖测定，发现表达p14 ARF（NPM 1的拮抗剂）的MDAH 041细胞显示依赖于p27诱导的生长抑制。此外，为了研究p27在非锚定培养条件下的功能，我们进行了软琼脂集落形成试验，观察到携带野生型p53（一种主要肿瘤抑制因子）的一些细胞系的殖民地形成受到p27诱导的抑制。这些结果表明，在锚定依赖性和锚定非依赖性培养条件下，p27功能在癌细胞类型中受到差异调节。
p27Kip1is known as a major cyclin‐dependent kinase inhibitor and a tumor suppressor, and often functionally hampered at protein level. p27 protein expression levels are frequently low in various cancers and negatively correlated with malignancy of cancer. However, in our previous study, we discovered that p27 overexpression does not inhibit the proliferation of two cancer cell lines due to a functional suppression of p27 by nucleophosmin isoform 1 (NPM1); that is, a qualitative, not quantitative, suppression of p27 function occurs in these cancer cell lines. To clarify the regulation of p27 in several types of cancer, we investigated p27 function in other cancer cell lines, based on proliferation assays in those cell lines carrying doxycycline‐inducible p27, and found that MDAH041 cells which express p14ARF, an antagonist of NPM1, show growth inhibition depending on p27 induction. Moreover, to investigate p27 function under anchorage‐independent culture conditions, we performed soft agar colony formation assay and observed that the colony formation of some cell lines carrying wild‐typep53, a major tumor suppressor, was inhibited depending on p27 induction. These results suggest that p27 function is regulated differentially among cancer cell types under anchorage‐dependent and anchorage‐independent culture conditions.