Tor Receptor Research Articles

The impact of hormone receptor status on survival and recurrence of HER2-positive breast cancers in standard adjuvant setting: A retrospective study in Tehran, Iran.

To evaluate hormone receptor status on survival and recurrence of the human epidermal growth factor receptor 2-positive breast cancer treated with Trastuzumab in the adjuvant setting. The retrospective study was conducted in 2017 at the Breast Cancer Research Centre, Tehran University of Medical Sciences, Tehran, Iran, and comprised data of women aged >20 years with stage I-III of human epidermal growth factor receptor 2-positive breast cancer who were treated with Trastuzumab from 2008 to 2017. The patients were divided into two groups. Group P had patients who were triple positive for human epidermal growth factor receptor 2, oestrogen receptor and progesterone receptor. Group N had patients positive for only human epidermal growth factor receptor 2. All patients in group P were treated with hormone therapy. Overall survival, disease-free survival, and distant metastasis rates were measured. SPSS 22 was used for data analysis. Of the 263 patients, 169(%) were in group P with a mean age of 46.86 ± 10.92 years, and 94(%) were in group N with a mean age of 48.53±12.33 years (p>0.05). There were no unfavourable predictors for overall survival and disease-free survival except for stage (p<0.05). The difference on both counts between the groups was not significant (p>0.05 each). The impact of hormone receptor positivity on survival and progression of human epidermal growth fac tor receptor 2-positive breast cancer remains an area of debate.

Accumulation of the Drosophila Torso-like protein at the blastoderm plasma membrane suggests that it translocates from the eggshell.

The eggshell serves as a depository for proteins that play an important role in early embryonic development. In particular, the Drosophila eggshell is responsible for transferring asymmetries from the egg chamber to specify the regions at both ends of the embryo through the uneven activation of the Torso (Tor) receptor in its membrane. This process relies on the restricted expression of the gene torso-like (tsl) in subpopulations of follicle cells during oogenesis and its protein accumulation at both poles of the eggshell, but it is not known how this signal is transmitted to the embryo. Here, we show that Tsl accumulates at the embryonic plasma membrane, even in the absence of the Tor receptor. However, during oogenesis, we detected Tsl accumulation only at the eggshell. These results suggest that there is a two-step mechanism to transfer the asymmetric positional cues from the egg chamber into the early embryo: initial anchoring of Tsl at the eggshell as it is secreted, followed by its later translocation to the egg plasma membrane, where it enables Tor receptor activation. Translocation of anchored determinants from the eggshell might then regulate the spatial and temporal control of early embryonic developmental processes.

Human papillomavirus in rare unilateral benign intranasal tumours

Inverted papilloma (IP), oncocytic papilloma (OP), respiratory epithelial adenomatoid hamartoma (REAH) and capillary hemangioma (CH) are benign and rare tumours. OP and IP are associated with squamous cell carcinoma (SCC). Human papillomavirus (HPV) may play a role in malignant transformation. We aimed to investigate the presence of HPV, inflammation, epithelial dysplasia, and prognostic markers including proliferative cell nuclear antigen (PCNA), epidermal growth fac- tor receptor (EGFR) and p53 in tissue specimens from rare unilateral intranasal benign tumours. Presence of HPV DNA was detected by PCR. Proliferative cell nuclear antigen, EGFR, p53 expression and the presence of HPV type 16 in tissues were determined by immuno-histochemical analysis. We determined the presence of HPV DNA in 2 of 6 IP cases, in one CH patient and one OP patient, but the REAH patient was negative. Histologically, only one specimen with IP was positive for HPV type 16 being the high risk type. The remaining cases were considered as low risk type HPV. Although our patient numbers are limited, there is a significant association between IP and HPV. This is the first study showing the cooccurrence of CH and OP with HPV.

Quantitative variations in the level of MAPK activity control patterning of the embryonic termini in Drosophila.

We have examined the role in patterning of quantitative variations of MAPK activity in signaling from the Drosophila Torso (Tor) receptor tyrosine kinase (RTK). Activation of Tor at the embryonic termini leads to differential expression of the genes tailless and huckebein. We demonstrate, using a series of mutations in the signal transducers Corkscrew/SHP-2 and D-Raf, that quantitative variations in the magnitude of MAPK activity trigger both qualitatively and quantitatively distinct transcriptional responses. We also demonstrate that two chimeric receptors, Torextracellular-Egfrcytoplasmic and Torextracellular-Sevcytoplasmic, cannot fully functionally replace the wild-type Tor receptor, revealing that the precise activation of MAPK involves not only the number of activated RTK molecules but also the magnitude of the signal generated by the RTK cytoplasmic domain. Altogether, our results illustrate how a gradient of MAPK activity controls differential gene expression and, thus, the establishment of various cell fates. We discuss the roles of quantitative mechanisms in defining RTK specificity.

Dissecting the mechanism of torso receptor activation

Regulated activation of receptor tyrosine kinases depends both on the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila the torso (tor) tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole which is trapped by the receptor, thereby impeding further diffusion. However, it is not well understood how this signal is generated, although it is known to depend on the activity of many genes such as torso-like ( tsl) and trunk ( trk). To further investigate the mechanism involved in the local activation of the tor receptor we have altered the normal expression of the tsl protein by generating females in which the tsl gene is expressed in the oocyte under the control of the tor promoter rather than in the ovarian follicle cells. Analysis of the phenotypes generated by this hybrid gene and its interactions with mutations in other genes in the pathway has enabled us to further dissect the mechanism of tor receptor activation and to define more precisely the role of the different genes acting in this process.

Intercellular signaling and the polarization of body axes during Drosophila oogenesis.

The anterior-posterior and dorsal-ventral axes of the Diosophila egg and embryo are established during oogen­ esis as the egg is being formed. The mechanisms under­ lying this process involve intercellular signaling events, including bidirectional communication between germline and somatic cells, and local cell-cell interactions in the soma. On the molecular level, these interactions ap­ pear to be mediated by a small number of intercellular signaling systems, including the Epidermal growth fac­ tor receptor [Egfr] and Notch systems, that are used mul­ tiple times during oogenesis to trigger different develop­ mental switches. The precisely regulated interplay be­ tween these various signaling systems forms a network of interdependencies that leads to the establishment of both the anterior-posterior and dorsal-ventral polarity in the egg chamber and embryo. Because both the Egfr and Notch signaling systems are widely conserved, the mechanisms involved in the regulation of these pro­ cesses in Drosophila oogenesis may serve as a paradigm for understanding intercellular signaling events in other organisms.

Similarities between trunk and spätzle, putative extracellular ligands specifying body pattern in Drosophila.

The basic body plan of Drosophila is specified by four determinant systems that organize pattern along the anteroposterior and dorsoventral axes. Two of these systems (anterior and posterior) depend on localized mRNAs. In contrast, the other two (ventral and terminal) require locally generated extracellular ligands that are transduced, respectively, by the transmembrane receptors Toll and torso (tor). The ligand for the Toll receptor is thought to be spätzle (spz), a secreted protein that is activated by proteolytic cleavage. Here we report that trunk (trk), a gene required for activity of the tor receptor, encodes a protein that resembles spz in several respects. In particular, the sequence suggests that trk is a secreted protein and that it contains an internal site for proteolytic cleavage. Furthermore, the carboxy-terminal domain of trk has a similar arrangement of cysteines to that of spz. We propose that trk encodes an extracellular ligand involved in specifying terminal body pattern and suggest by analogy with spz that a cleaved form of trk constitutes the ligand for the tor receptor.