Notch pathway is activated by MAPK signaling and influences papillary thyroid cancer proliferation.

Mutually exclusive genetic alterations in the RET, RAS, or BRAF genes, which result in constitutively active mitogen-activated protein kinase (MAPK) signaling, are present in about 70% of papillary thyroid carcinomas (PTCs). However, the effect of MAPK activation on other signaling pathways involved in oncogenic transformation, such as Notch, remains unclear. In this study, we tested the hypothesis that the MAPK pathway regulates Notch signaling and that Notch signaling plays a role in PTC cell proliferation. Conditional induction of MAPK signaling oncogenes RET/PTC3 or BRAF(T1799A) in normal rat thyroid cell line mediated activation of Notch signaling, upregulating Notch1 receptor and Hes1, the downstream effector of Notch pathway. Conversely, pharmacological inhibition of MAPK reduced Notch signaling in PTC cell. Thyroid tumor samples from transgenic mice expressing BRAF(T1799A) and primary human PTC samples showed high levels of Notch1 expression. Down-regulation of Notch signaling by γ-secretase inhibitor (GSI) or NOTCH1 RNA interference reduces PTC cell proliferation. Moreover, the combination of GSI with a MAPK inhibitor enhanced the growth suppression in PTC cells. This study revealed that RET/PTC and BRAF(T1799A) activate Notch signaling and promote tumor growth in thyroid follicular cell. Taken together, these data suggest that Notch signaling may be explored as an adjuvant therapy for thyroid papillary cancer.

Inheritance of Anthracnose Resistance in Common Bean Differential Cultivar AB 136.

Inheritance of anthracnose resistance of the common bean (Phaseolus vulgaris L.) differential cultivar AB 136 to races 89, 64, and 73 (binary system designation) was studied in crosses with the susceptible differential cultivars Michelite (race 89), Mexico 222 (race 64), and Cornell 49-242 (race 73). In each cross two progenitors, the F1, F2, and backcross-derived plants were inoculated with the respective race under environmentally controlled greenhouse conditions. The results indicate that single dominant gene(s) control resistance to races 89 and 64, giving a segregation ratio of 3:1 in the F2, 1:0 in the backcrosses to AB 136, and 1:1 in the backcross to Michelite (race 89), and to Mexico 222 (race 64). For race 73, the following segregation ratios between resistant and susceptible plants were observed: 13:3 in the F2, 1:0 in the backcross to AB 136, and 1:1 in the backcross to Cornell 49-242. Such results suggest that two independent genes may determine resistance of AB 136 to race 73, one dominant (Co-6) and one recessive that is proposed to be assigned co-8. Genotypes Co-6_ or co-8 co-8 would condition resistance, whereas susceptibility would be present in genotypes co-6 co-6 Co-8_. Given the dominant nature of anthracnose resistance genes present in line AB 136 and its resistance to 25 races of Colletotrichum lindemuthianum identified in Brazil by other researchers, we included this cultivar as one of the donor parents in our molecular marker-assisted backcross breeding program, to develop common bean cultivars resistant to anthracnose and adapted to Central Brazil.