Transducer Of ERBB2 Research Articles

Tob deficiency superenhances osteoblastic activity after ovariectomy to block estrogen deficiency-induced osteoporosis.

Tob (transducer of erbB2) is a member of antiproliferative family proteins and acts as a bone morphogenic protein inhibitor as well as a suppressor of proliferation in T cells, which have been implicated in postmenopausal bone loss. To determine the effect of Tob deficiency on estrogen deficiency-induced bone loss, we analyzed bone metabolism after ovariectomy or sham operation in Tob-deficient mice. Ovariectomy in WT mice decreased trabecular bone volume and bone mineral density (BMD) as expected. In Tob-deficient mice, ovariectomy reduced bone volume and BMD. However, even after ovariectomy, both trabecular bone volume and BMD levels in Tob-deficient bone were comparable to those in sham-operated WT bones. Bone formation parameters (mineral apposition rate and bone formation rate) in the ovariectomized Tob-deficient mice were significantly higher than those in the ovariectomized WT mice. In contrast, the ovariectomy-induced increase in the bone resorption parameters, osteoclast surface, and osteoclast number was similar between Tob-deficient mice and WT mice. Furthermore, in ex vivo nodule formation assay, ovariectomy-induced enhancement of nodule formation was significantly higher in the bone marrow cells from Tob-deficient mice than in the bone marrow cells from ovariectomized WT mice. Both Tob and estrogen signalings converge at bone morphogenic protein activation of alkaline phosphatase and GCCG-reporter gene expression in osteoblasts, revealing interaction between the two signals. These data indicate that Tob deficiency prevents ovariectomy-induced bone loss through the superenhancement of osteoblastic activities in bone and that this results in further augmentation in the bone formation rate and the mineral apposition rate after ovariectomy in vivo.

Алогенний скринінг пухлинних антигенів з кДНК бібліотек раку щитовидної залози

© 2004, National Academy of Sciences of Ukraine. All rights reserved. The search for novel tumor-associated antigens eliciting humoral and cellular immune responses in tumor patients is an important goal in cancer diagnosis and immunotherapy. We utilized SEREX immunoscreening methodology to identify a set of novel tumor antigens, associated with thyroid cancer. 16 distinct antigens reactive with autologous sera were identified by SEREX analysis of two cDNA libraries from patients with papillar carcinoma of thyroid gland. SEREX-defined antigens were evaluated by allogenic screening with sera samples from normal donors, patients with thyroid, colon and breast cancer. The analysis showed that 8 antigens reacted exclusively with autologous sera, 2 antigens (KY-THY-25 and KY-THY-40) were recognized by sera from patients with thyroid and breast cancer (10 % and 2.4 % respectively) while the other antigens cross-reacted with the sera from both normal donors and cancer patients. KY-THY-17 (zinc finger protein), KY-THY-28 (transducer of ERBB2) and KY-THY-29 (solid tumor associated protein) exhibited high immunoreactivity with sera from patients with thyroid, breast and colon cancer, when compared with the sera from normal donors. These antigens are potential candidates for the development of novel diagnostic and immunotherapeutic approaches in cancer.

Gene expression differences in bipolar disorder revealed by cDNA array analysis of post-mortem frontal cortex.

Previous studies have implicated a number of biochemical pathways in the etiology of bipolar disorder (BD). However, the precise abnormalities underlying this disorder remain to be established. To investigate novel factors that may be important in the pathophysiology of BD, we utilized cDNA expression arrays to examine differences in expression of up to 1200 genes known to be involved in potentially relevant biochemical processes. This investigation was undertaken in post-mortem samples of frontal cortex tissue from patients with BD and matched controls, obtained (n = 10/group) from the Stanley Foundation Neuropathology Consortium. Results include significant (greater than 35% change in signal intensity) differences between BD and controls in a number of genes (n = 24). Selected targets were analyzed by RT-PCR, which confirmed a decrease in transforming growth factor-beta1 (TGF-beta 1), and an increase in both caspase-8 precursor (casp-8) and transducer of erbB2 (Tob) expression in BD. We further observed a significant decrease of TGF-beta 1 mRNA levels in BD by RT-PCR in individual post-mortem samples. Given the neuroprotective role attributed to this inhibitory cytokine, our results suggest that the down-regulation of TGF-beta 1 may lead to various neurotoxic insults potentially involved in the etiology of certain mood disorders.

Inhibition of human pancreatic cancer growth by the adenovirus-mediated introduction of a novel growth suppressing gene, tob, in vitro.

Tob (Transducer of ErbB-2) is a newly identified tumor suppressor that may interact/interfare with protein tyrosine kinase receptors including ErbB-2 [1]. ErbB-2 phosphorylates and interacts with Shc that participates inbetween active tyrosine protein kinases to Ras signaling pathway. A point mutation or an elevated expression of ErbB-2 results in oncogenic growth of cells.KeywordsPancreatic Cancer Cell LineRecombinant AdenovirusHuman Pancreatic Cancer Cell LineRecombinant Adenovirus VectorActive Tyrosine Protein KinaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.