Anti-SPRY1 (aa 1-110) polyclonal antibody

Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we reported that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) [Oncogene, 2010, 29: 5241-5253]. In general, various studies established inhibition of cell proliferation by SPRY in cancer. The mechanisms by which SPRY regulates cell proliferation in CRC are investigated. We demonstrate, for the first time, suppression of SPRY2 augmented EGF-dependent oncogenic signaling, however, surprisingly decreased cell proliferation in colon cancer cells. Our data suggest that cell cycle inhibitor p21(WAF1/CIP1) transcriptional activity being regulated by SPRY2. Indeed, suppression of SPRY2 significantly increased p21(WAF1/CIP1) mRNA and protein expression as well as p21(WAF1/CIP1) promoter activity. Conversely, overexpressing SPRY2 triggered a decrease in p21(WAF1/CIP1) promoter activity. Concurrent down-regulation of both SPRY1 and SPRY2 also increased p21(WAF1/CIP1) expression in colon cancer cells. Increased nuclear localization of p21(WAF1/CIP1) in SPRY2 downregulated colon cancer cells may explain the inhibition of cell proliferation in colon cancer cells. Underscoring the biological relevance of these findings in SPRY1 and SPRY2 mutant mouse, recombination of floxed SPRY1 and SPRY2 alleles in mouse embryonic fibroblasts (MEFs) resulted in increased expression and nuclear localization of p21(WAF1/CIP1) and decreased cell proliferation. In CRC, the relationship of SPRY with p21 may provide unique strategies for cancer prevention and treatment. (c) 2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

The temporomandibular joint is a highly conserved articulation because it promotes survival and propagation via the essential functions of mastication, communication, and routine mating success (dentofacial esthetics). The temporomandibular joint is a unique secondary joint formed between the endochondral temporal bone and the mandibular secondary condylar cartilage via Indian hedgehog and bone morphogenetic protein signaling that is closely related to ear development. A dynamic epigenetic environment is provided by Spry1 and Spry2 genetic induction of the lateral pterygoid and temporalis muscles. Mechanical loading of the condylar periosteum during fetal development produces a superficial layer of fibrocartilage that separates from the condyle to form the interposed temporomandibular joint disc. The articular surfaces of the condyle and fossa are dynamically modified periosteum that has healing and regenerative capability. This unique tissue is composed of a superficial fibrous layer (synovial surface) with an underlying proliferative (cambium) layer that produces a cushioning layer of fibrocartilage which subsequently forms bone. Prior to occlusion of the first primary (deciduous) molars at about 16 months, facial development is dominated by primary genetic mechanisms. After achieving posterior functional occlusion, biomechanics enhances temporomandibular joint maturation, and assumes control of facial growth, development and adaptation. Concurrently, hypothalamus control of musculoskeletal physiology shifts from insulin-like growth factor IGF2 to IGF1, which affects bone via muscular loading (biomechanics). Three layers of temporomandibular joint fibrocartilage are resistant to heavy functional loading, but parafunctional clenching may result in degeneration that is first manifest as trabecular sclerosis of the mandibular condyle.