Biomedical subjects

Kotaro Azuma

Publications and source records attributed to Kotaro Azuma.

4 recordsLinked to original sources

PubMed2005

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma.

To acquire information on signal alteration corresponding to the changes in metastatic potential, we analysed protein tyrosine phosphorylation of low- and high-metastatic human osteosarcoma HuO9 sublines, which were recently established as the first metastatic model of human osteosarcoma. Tyrosine phosphorylation of proteins around 60, 70, and 120-130 kDa was enhanced in high-metastatic sublines. Among these proteins, the protein around 70 kDa, which was most remarkably phosphorylated, was identified as paxillin, a scaffold protein in integrin signaling. Activity of Src family kinase correlated well with metastatic potential, and a Src family kinase inhibitor, PP2, not only abolished tyrosine phosphorylation of paxillin but also impaired the motility of high-metastatic sublines. The expression of paxillin was also elevated in high-metastatic sublines, and knocking down of paxillin expression by RNAi method resulted in attenuated motility of high-metastatic cells. We also demonstrated that the phosphorylated form of paxillin is essential for the migration-promoting effect in human osteosarcoma. These findings suggest that enhanced activity of Src family kinases and overexpression of paxillin synergistically contribute to the high metastatic potential of human osteosarcoma through the hyperphosphorylation of paxillin.

Animals↗

PubMed2004

Analysis of estrogen receptor alpha signaling complex at the plasma membrane.

There is accumulating evidence that the estrogen receptor (ER) can transduce specific signals at the plasma membrane. We tried to clarify the biological function of ER as a signaling molecule by identifying proteins that interact with the membrane-localized ER. The activation function 1 and 2 (AF-1 and AF-2) domains of ERalpha with or without the membrane-targeting sequence were stably expressed in the breast cancer cell line, MCF-7. The level of tyrosine phosphorylation of AF-2 was significantly elevated by the membrane localization. By mass-spectrometry analysis, alpha- and beta-tubulins and heat shock protein 70 were identified as the AF-1-associated proteins. Of these, tubulins are associated only with membrane-targeted AF-1.

Antibodies, Monoclonal↗

PubMed2004

[Hormone replacement therapy].

Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen for postmenopausal women. Usually progestin is used in combination to avoid endometrial proliferation. As for bone metabolism, estrogens exert bone protective effect through inhibition of bone absorption. HRT has been shown to improve bone mineral density and to lower the risk of osteoporotic bone fracture. However, the results of recent large scale clinical studies in the U.S. indicate that HRT not only raise the risk of breast cancer, but also increase the incidence of atherosclerotic cardiovascular diseases. According to these studies, the benefit of HRT does not outweigh its risk except the treatment of postmenopausal vasomotor symptoms. To resolve this problem, low dose HRT and SERM (selective estrogen receptor modulator) regimens are under investigation.

Adolescent↗

PubMed2004

[Selective estrogen receptor modulators: mechanisms of action and their tissue selectivity].

The SERMs (Selective Estrogen Receptor Modulators) exert selective agonistic or antagonistic effects on various estrogen target tissues. Conformational change of SERM-bound Estrogen Receptor (ER) and tissue specific expression patterns of transcription co-factors have been well investigated as the underlying factors of tissue selectivity of the SERMs. Nongenomic action, modulation of protein levels of ER and co-factors, and activation of other nuclear receptors, have been also reported as mechanisms of tissue selectivity by SERMs.

Animals↗