GKLF in thymus epithelium as a developmentally regulated element of thymocyte-stroma cross-talk

Panigada, Maddalena; Porcellini, Simona; Sutti, Francesca; Doneda, Luisa; Pozzoli, Ombretta; Consalez, G. Giacomo; Guttinger, Maria; Grassi, Fabio

doi:10.1016/s0925-4773(98)00237-8

Cited by 46 publications

(39 citation statements)

References 60 publications

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“…Consistent with its tissue distribution, KLF4 has been shown to be imperative for terminal differentiation of keratinocytes of the skin (Segre et al, 1999) and goblet cells of the intestines (Katz et al, 2002). In the thymus, KLF4 is expressed during cortical differentiation suggesting a role in T-lymphocyte differentiation (Panigada et al, 1999). KLF4 is also highly expressed in the testes, specifically in the postmeiotic germ cells and somatic Sertoli cells, suggesting an important role in testicular differentiation (Behr and Kaestner, 2002).…”

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confidence: 83%

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

et al. 2003

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Kru¨ppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor, the expression of which is enriched in the postmitotic cells of the intestinal epithelium. KLF4 is a target gene of the tumor suppressor adenomatous polyposis coli (APC). We sought to determine the role of KLF4 in suppressing the tumorigenecity of RKO colon cancer cells, which do not express KLF4. We utilized an established system in RKO cells, in which an inducible promoter controls expression of KLF4. Four independent assays were used to assess the effects of KLF4 induction on tumor cells. We find that KLF4 overexpression reduces colony formation, cell migration and invasion, and in vivo tumorigenecity. The mechanism of action of KLF4 does not involve apoptosis. These findings, along with our previous findings that KLF4 induces G1/S arrest, suggest that KLF4 is a cell cycle checkpoint protein that can reduce tumorigenecity of colon cancer cells.

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confidence: 83%

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

et al. 2003

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“…5,6 Later, it was found in a variety of other tissues, such as thymus, cornea, cardiac myocytes and lymphocytes. [7][8][9][10] KLF4 has an important role in the development and cell differentiation. 6,11,12 In normal lung tissue, KLF4 is expressed in fibroblasts and airway epithelial cells, and was found to be the most significantly altered lung gene at birth.…”

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confidence: 99%

KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer

Chen

Zhang

et al. 2015

Cell Death Differ

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Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifeninduced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras LSL-G12D/+ ;Klf4 fl/fl mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

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“…The product of Nanog is also known as a core pluripotency factor (Mitsui et al, 2003;Silva et al, 2006). These genes are active in ES cells, but inactive in hepatocytes (Panigada et al, 1999;Mitsui et al, 2003;Amaral et al, 2009;Tanase et al, 2011). The Cyp7α1, Pck1, Tat and Tdo2 genes are strongly expressed in hepatocytes differentiated from mouse ES cells, and thus, they are used as differentiation markers (Teratani et al, 2005;Banas et al, 2007;Tanase et al, 2011 Table 1.…”

Section: Resultsmentioning

confidence: 99%

Positions of pluripotency genes and hepatocyte-specific genes in the nucleus before and after mouse ES cell differentiation

Udagawa

Ohyama

2014

Genet. Mol. Res.

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ABSTRACT. Spatial positioning of genes in the cell nucleus plays an important role in the regulation of genomic functions. Evidence for changes in gene positioning associated with transcriptional activity has been reported. However, our understanding of this phenomenon is still quite limited. We examined how pluripotency genes and hepatocytespecific genes behave during the differentiation of mouse embryonic stem (ES) cells into hepatocytes, by targeting the loci of the Klf4, Nanog, Oct4, Sox2, Cyp7α1, Pck1, Tat, and Tdo2 genes, and using three-dimensional fluorescence in situ hybridization analyses. We found that each gene has a distinctly inherent localization profile in the ES cell nucleus. During differentiation, the Klf4, Nanog, Oct4, Cyp7α1, Pck1, and Tat loci shifted toward the nuclear center, while the Sox2 and Tdo2 loci shifted toward the periphery. The Klf4, Nanog, Oct4, and Tdo2 seem to prefer the outer regions, rather than the inner regions, when they are active. We also found that the radial positioning of the focused genes in the hepatocyte cell nucleus was highly correlated with 1980 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (1) : 1979-1988 (2014) K. Udagawa and T. Ohyama the local GC content and the gene density of the surrounding region, but not with gene activity.

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GKLF in thymus epithelium as a developmentally regulated element of thymocyte-stroma cross-talk

Cited by 46 publications

References 60 publications

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer

Positions of pluripotency genes and hepatocyte-specific genes in the nucleus before and after mouse ES cell differentiation

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