RESUMEN
Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.
Asunto(s)
Proteínas de Plantas , Transducción de Señal , Estrés Fisiológico , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas/genética , Plantas/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Calcio/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The transforming growth factor beta (TGF-beta) is a vital regulator of placental development and functions. TGF-beta exerts several modulatory effects on trophoblast cells, such as inhibition of proliferation and invasiveness, and stimulation of differentiation by inducing multinucleated cell formation. In this study, we determine the expression patterns of TGF-beta signaling molecules in normal trophoblast, various hydatidiform mole types and choriocarcinoma. A total of 132 cases, including 51 normal placenta (20 first trimester, 11 second trimester, and 20 third trimester) and 81 gestational trophoblastic diseases (17 choriocarcinoma, and 64 hydatidiform moles: 39 complete, 6 partial, and 19 invasive) were immunohistochemically analyzed with anti-TGF beta1/2, TGF-beta receptor type I (TbetaRI), TbetaRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-beta signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-beta signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-beta signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TbetaRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TbetaRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-beta signaling pathway plays an important role in the pathogenesis and progression of gestational trophoblastic disease, and may thus be employed as a potential therapeutic target and a diagnostic biomarker.
Asunto(s)
Coriocarcinoma/metabolismo , Mola Hidatiforme/metabolismo , Placenta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Neoplasias Uterinas/metabolismo , Receptores de Activinas Tipo I/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Coriocarcinoma/patología , Femenino , Edad Gestacional , Humanos , Mola Hidatiforme/patología , Técnicas para Inmunoenzimas , Placenta/patología , Embarazo , Proteínas Serina-Treonina Quinasas , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Smad/metabolismo , Análisis de Matrices Tisulares , Neoplasias Uterinas/patologíaRESUMEN
Gallbladder carcinomas are rare but highly lethal neoplasms. We examined the expression of five cell-cycle-related molecules (p53, RB, cyclin D1, p27, Ki-67), and MSH2, in 46 carcinomas, 14 adenomas, 15 low-grade dysplasias, 9 intestinal metaplasias and 20 normal gallbladder epithelia. The expression of these molecules was altered in gallbladder carcinomas and adenomas. In gallbladder carcinomas we observed increased expression of p53, cyclin D1, Ki-67, and MSH2 together with decreased expression of RB and p27 protein. Aberrant expression of cyclin D1 and reduced expression of RB were noted in adenomas, and expression of cyclin D1 was elevated in low-grade dysplasias. However, there was no change in the levels of these cell-cycle molecules in metaplasia. Expression of p53, p27, Ki-67, and MSH2 was correlated with clinical stage (P<0.05) and there was also a correlation between the expression of Ki-67 and MSH-2 and patient age (P<0.05). These results suggest that altered expression of cell-cycle molecules p53, cyclin D1, RB, p27, and of MSH-2 is involved in the progression of gallbladder carcinomas.
