Interferon-γ modulates terminal differentiation and the expression of desquamin in cultured keratinocytes

Brysk, Miriam M.; Bell, Trace; Hoida, Chana; Tyring, Stephen K.; Rajaraman, Srinivasan

doi:10.1016/0014-4827(91)90415-q

Cited by 23 publications

(15 citation statements)

References 18 publications

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“…Experimental evidence has demonstrated that NBS1 is translocated into the nucleus by importin KPNA2, which mediates NBS1 subcellular localization and its functions in tumorigenesis, as part of the MRE11–RAD50–NBS1 complex. 33 However, we did not find changes in NBS1 expression or location in KPNA2-knockdown and -overexpressing EOC cells. We speculate that KPNA2 may contribute to other mechanisms in Akt activation, which require further investigation.…”

Section: Discussioncontrasting

confidence: 70%

“…Expression of KPNA2 was specifically regulated by TGF- β 1 and IFN- γ : TGF- β 1 induced reversible growth arrest at the G1 phase of the cell cycle, 30, 31, 32 while IFN- γ induced irreversible growth arrest in cultured keratinocytes and promoted aberrant terminal differentiation. 33 In addition, KPNA2 is a target of c-Myc; the expression and nuclear localization of c-Myc is rapidly downregulated when keratinocytes are treated with TGF- β 1. 34, 35 In addition, the transcription factor c-Myc downregulates p21Cip1 and p27Kip1, and upregulates cyclin D1 at the transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

“…38 In the current study, we found that KPNA2 knockdown decreased the level of phosphorylated Akt and phosphorylated FOXO3a, indicating that downregulation of KPNA2 may arrest EOC cells at the G1 phase through the Akt/FOXO3a pathway. A study by Brysk et al 33 reported that the MRE11–RAD50–NBS1 complex serves as a sensor and a mediator in cell cycle checkpoint signaling. NBS1 functions as a tumor suppressor by preserving genome integrity in the nucleus, and may also have an oncogenic role in the cytoplasm associated with the PI3-kinase/Akt-activation pathway.…”

Section: Discussionmentioning

confidence: 99%

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KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a

Huang

et al. 2013

Cell Death Dis

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Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, has a central role in nucleocytoplasmic transport and is overexpressed in many cancers. Our previous study identified KPNA2 as significantly upregulated in epithelial ovarian carcinoma (EOC), correlating with poor survival of patients. However, the precise mechanism of this effect remains unclear. The aim of the present study was to examine the role of KPNA2 in the proliferation and tumorigenicity of EOC cells, and its clinical significance in tumor progression. Real-time quantitative RT-PCR analysis revealed high expression levels of KPNA2 in 162 out of 191 (84.8%) fresh EOC tissues, which was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, differentiation, histological type, recurrence, and prognosis of EOC patients. Our results showed that upregulation of KPNA2 expression significantly increased the proliferation and tumorigenicity of EOC cells (EFO-21 and SK-OV3) in vitro and in vivo, by promoting cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. By contrast, knockdown of KPNA2 effectively suppressed the proliferation and tumorigenicity of these EOC cells in vitro and in vivo. Our results also indicated that the molecular mechanisms of the effect of KPNA2 in EOC included promotion of G1/S cell cycle transition through upregulation of c-Myc, enhanced transcriptional activity of c-Myc, activation of Akt activity, suppression of FOXO3a activity, downregulation of cyclin-dependent kinase (CDK) inhibitor p21Cip1 and p27Kip1, and upregulation of CDK regulator cyclin D1. Our results show that KPNA2 has an important role in promoting proliferation and tumorigenicity of EOC, and may represent a novel prognostic biomarker and therapeutic target for this disease.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a

Huang

et al. 2013

Cell Death Dis

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“…Of potential relevance to the fragile equilibrium between epithelial colonization and infection, IFN-␥ promotes expression of the glycoprotein desquamin, a cell adhesion molecule in the stratum corneum of the human epidermis which possesses lectin-like properties for amino sugars (58), as well as trypsin-like serine proteinase (57) and RNase (393) activity. Desquamin may thus play a crucial role in desquamation and shedding of Candida from the superficial portion of the epithelium.…”

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confidence: 99%

Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

2004

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Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4+ cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8+ T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal

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“…IFN-a) and type II interferon (IFN-g) has been studied for the past two decades [13][14][15]. Many early studies were primarily focused on immunological parameters such as induction of various MHC class I or class II molecules on the cell surface [16], and/or adhesion molecules (e.g.…”

Section: Introductionmentioning

confidence: 99%

Knock down of p53 levels in human keratinocytes increases susceptibility to type I and type II interferon-induced apoptosis mediated by a TRAIL dependent pathway

Chaturvedi

Bodner

Qin

et al. 2006

Journal of Dermatological Science

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Interferon-γ modulates terminal differentiation and the expression of desquamin in cultured keratinocytes

Cited by 23 publications

References 18 publications

KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a

KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a

Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

Knock down of p53 levels in human keratinocytes increases susceptibility to type I and type II interferon-induced apoptosis mediated by a TRAIL dependent pathway

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