Alternative splicing represents a unique post-transcriptional mechanism that increases the complexity of the eukaryotic proteome-generating protein isoforms whose functions can be novel, diverse, and/or even antagonistic when compared to its full-length transcript. The KLF family of genes consists of ≥17 members, which are involved in the regulation of numerous critical cellular processes, including differentiation, cell proliferation, growth-related signal transduction, angiogenesis, and apoptosis. Using a strategy based on RT-PCR, selective cloning, and promoter-based assays of cancer-relevant genes, we identify and characterize the existence of multiple biologically active KLF splice forms across the entire family of proteins. We demonstrate biological function for a number of these isoforms. Furthermore, we highlight a possible functional interaction between full-length KLF4 and one of its splice variants in up-regulating cellular proliferation. Taken together, this report identifies for the first time a more complete view of the genomic and proteomic breadth and complexity of the KLF transcription factor family, revealing the existence of highly expressed and biologically active isoforms previously uncharacterized. In essence, knowing that these KLF isoforms exist provides the first step toward understanding the roles of these genes in human health and disease.
Objective: To report an unusual paraneoplastic syndrome, amyotrophic lateral sclerosis, associated with renal cell carcinoma. Case Presentation and Intervention: A 59-year-old man presented with muscle weakness and fasciculations in the upper extremities. Neurological examination showed that the fasciculations arose spontaneously in the upper limbs. Electrodiagnostic studies revealed an active neurogenic disorder. The patient was diagnosed with a motor neuron disease mimicking amyotrophic lateral sclerosis. Urine analysis revealed microscopic hematuria. Abdominal computerized tomography scans showed a 9.5 × 8 cm renal mass in the lower pole of the right kidney. Curative right radical nephrectomy was performed. Pathologic examination showed a clear cell adenocarcinoma. After nephrectomy, the muscle weakness and fasciculations disappeared spontaneously within 2 months. The patient was disease-free for 58 months after right radical nephrectomy. He complained of muscle weakness and fasciculation at the last follow-up again. Physical examination revealed fasciculation in the upper limbs. Abdominal tomography showed a 22 × 20 mm solid mass in the lower pole of the left kidney. Kidney-saving surgery was performed and the diagnosis of renal cell carcinoma was confirmed pathologically. Following surgery, fasciculations completely disappeared and muscle weakness diminished within 3 months. Conclusion: This case highlights motor neuron disease as a rare paraneoplastic syndrome in association with renal cell carcinoma and resolution after removal of the tumor.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.