Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID6 (Kruppel-like)
 147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kruppel-like factors (KLFs) are a group of transcription factors that appear to be involved in different biological processes including carcinogenesis. In a recent study, KLF6 was reported as a tumor suppressor gene in prostate cancer because of its frequent loss of heterozygosity (LOH) and mutation as well as functional suppression of cell proliferation. Loss of chromosomal locus spanning KLF6 is relatively infrequent in other published studies of prostate cancer, however. To clarify the role of KLF6 in prostate cancers, particularly those that are high grade, we examined KLF6 for deletion, mutation, and loss of expression in 96 prostate cancer samples including 21 xenografts/cell lines. Loss of heterozygosity occurred in 4 (19%) of 21 xenografts/cell lines and 8 (28%) of 29 informative tumors. Fourteen of the 96 (15%) samples showed 15 somatic sequence changes in the KLF6 gene, including 7 that changed KLF6 peptide sequences, 4 that did not, and 4 that were located in untranslated regions. Expression levels of KLF6 were significantly lost in 4 of 20 (20%) xenografts/cell lines of prostate cancer, as detected by RT-PCR and Northern blot analysis. These findings indicate that significant genetic alterations of KLF6 occur in a minority of high-grade prostate cancers.
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PMID:Deletion, mutation, and loss of expression of KLF6 in human prostate cancer. 1265 97

The majority of human prostate cancers arise from the peripheral zone (PZ). Prostate epithelial stem cells have been localized to the basal epithelial cell compartment. In addition, basal cells have been shown to maintain luminal epithelial cell differentiation and may mediate signals between the stromal and luminal cell compartments. Therefore, the study of adult prostate basal cells derived from different prostate zones may give insights into the mechanisms underlying normal and abnormal prostate growth. We herein compare the basal and sex steroid-stimulated expression and activity of several genes/proteins that are known to be critical in prostate cancer development in primary cultures of basal cells derived from the transition zone (TZ) and PZ of prostatectomy specimens. Our results demonstrate that prostate basal cells derived from the PZ versus TZ are more viable in culture, particularly in response to sex steroid addition. PZ cells exhibit higher telomerase activity and increased expression levels of androgen receptor, the anti-apoptotic protein bcl-2, and the dominant-negative splice variant of Kruppel-like Factor 6. PZ cells have lower basal expression levels of estrogen receptor-beta, the pro-apoptotic protein Bax, and cell-cycle inhibitor proteins (p53, p21(waf1/Cip1)). Finally, we demonstrate divergent responses to sex hormones in the two basal cell populations. The gene expression pattern in the PZ cells may partially explain the predominance of prostate cancer development in this region.
Carcinogenesis 2006 Feb
PMID:Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones. 1612 18

ZNF217 is an alternatively spliced Kruppel-like transcription factor that has recently been implicated to play a role in human carcinogenesis. Here, we used immunohistochemistry (IHC) to show that ZNF217 protein is overexpressed in nearly 60% of ovarian tumor samples. The disease-free survival time was shorter in patients with positive ZNF217 expression than in ZNF217-negative patients (P=0.042). Fluorescence in situ hybridization (FISH) analysis showed ZNF217 genomic amplification in the poorly differentiated tumors, suggesting that ZNF217 is associated with the progression of ovarian cancer. Invasion was enhanced in HO-8910 cells stably transfected with constructs carrying full-length ZNF217 relative to cells transfected with the empty vector. To confirm our findings in vivo, we performed a tumorigenicity assay in nude mice inoculated with the HO-8910 overexpressing ZNF217 cells. As expected, tumors grown in the ZNF217 group were more invasive and prone to metastasis than those formed control groups. Based on these clinical and laboratory observations, we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes.
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PMID:ZNF217 is associated with poor prognosis and enhances proliferation and metastasis in ovarian cancer. 2503 22

We report the first 2 examples of primary renal myoepithelial carcinoma (MEC), both occurring in children. Both tumors had the unique morphologic features, immunophenotype, and EWSR1 gene rearrangements supporting the diagnosis. In keeping with the previous observations of an aggressive behavior in pediatric MEC, both cases presented with advanced local stage and distant metastases at the time of diagnosis. The EWSR1 translocation partner was identified as the Kruppel-like factor 15 (KLF15) gene in both tumors, and the novel EWSR1-KLF15 gene fusion transcripts were verified using reverse transcription polymerase chain reaction and Sanger dideoxy sequencing. So far, a role for KLF15 in carcinogenesis has not been established, in contrast to other members of the Kruppel-like family of transcription factors, and no rearrangements involving this gene have been documented to our knowledge. These findings expand the spectrum of pediatric renal tumors to include MEC. The characterization of novel EWSR1-KLF15 fusion transcripts carries important diagnostic implications, as well as clues to understand the pathogenesis of these neoplasms.
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PMID:Expanding the Spectrum of Renal Tumors in Children: Primary Renal Myoepithelial Carcinomas With a Novel EWSR1-KLF15 Fusion. 2652 41