Histology and histopathology Vol.25,nº10 (2010)
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- PublicationOpen AccessThe cellular expression of GABAA receptor a1 subunit during spermatogenesis in the mouse testis(Murcia : F. Hernández, 2010) Kanbara, Kiyoto; Okamoto, Keiko; Nomura, Sakashi; Kaneko, Takeshi; Watanabe, Masahito; Otsuki, YoshinoriGABAA receptors are pentamers in structure and are mainly composed of α, ß and γ subunits. These receptors are known to function as chloride channels. We observed α5, ß1 and γ3 subunit immunoreactivity in the mouse testes, specifically in the cytoplasm surrounding the nucleus in the spermatocytes and spermatids. In the current study, α1 subunit immunoreactivity was located in the nucleus of spermatogonia, spermatocytes and round spermatids. Immunoelectron microscopy revealed that the α1 subunit was localized within the nucleus of pachytene and diplotene spermatocytes in the area of condensed chromatin rather than extended chromatin. Protein sequence analysis revealed that the α1 subunit included DM DNA binding domains that were related to transcription factors involved in testicular differentiation in adult mice. These findings suggest that the α1 subunit may undertake a gene transcription function during the maturation of germ cells. α1 immunoreactivity was also detected within the mitochondria of spermatocytes and in the acrosome of round and elongated spermatids. Although the precise physiological role of the GABAA receptor α1 subunit in mitochondria remains unknown, we hypothesize that its function in the acrosome may be related to the acrosome reaction during fertilization or during spermatogenesis.
- PublicationOpen AccessNuclear accumulation of glioma-associated oncogene 2 protein and enhanced expression of forkhead-box transcription factor M1 protein in human hepatocellular carcinoma(Murcia : F. Hernández, 2010) Lin, M.; Guo, Lankai; Liu, H.; Du, J.; Yang, Jilong; Zhang, L.J.; Zhang, B.The hedgehog (Hh) signaling pathway has been reported to be crucial in human carcinogenesis and tumor progression. Glioma-associated oncogenes (Gli), are zinc finger transcription factors which mediate the transcriptional response to Hh signaling. To explore the role of Gli in the development and progression of hepatocellular carcinoma (HCC), we investigated the expression of Gli2 and FoxM1 (forkhead-box transcription factor M1) which is one of the Gli downstream target genes modulating cell cycle progression in 91 specimens of human HCCs with immunohistochemistry. These immunostaining results were compared with various clinicopathologic parameters. Immunoreactivity of Gli2 and FoxM1 was observed respectively in 84.6% (77/91) and 80.2% (73/91) cases of HCC tumor tissues, and this was considerably higher than expression in the peritumoral tissues. Distribution of Gli2 and FoxM1 proteins in tumor cells was nuclear with or without cytoplasmic staining, or cytoplasmic alone. Statistically, increased nuclear immunopositivity of Gli2 protein correlated significantly with poorer tumor differentiation (P<0.05), as well as with portal vein tumor thrombosis (P<0.05). In addition, overexpression of FoxM1 protein was significantly associated with increased tumor grade (P<0.01) and advanced tumor stage (P<0.05). Moreover, there was a significant association between the expressions of Gli2 and FoxM1 proteins in HCC (r=0.464, P=0.000). This is consistent with the concept that in human HCC, the Hh signaling pathway is involved in the differentiation and proliferation of tumor cells, in part through inducing nuclear accumulation of Gli2 protein and subsequent upregulation of FoxM1 protein.
- PublicationOpen AccessHuR, a key post-transcriptional regulator, and its implication in progression of breast cancer(Murcia : F. Hernández, 2010) Yuan, Zhu; Sanders, Andrew J.; Ye, Lin; Jiang, Wen G.HuR, an ubiquitously expressed member of the Hu family, selectively binds and stabilizes AREcontaining mRNAs encoding proto-oncogenes, cell cycle regulators, cytokines and growth factors. The mechanism of HuR stabilization on target mRNAs is believed to be mediated through competition with destabilizing ARE-BPs. HuR is mainly localized within the cell nucleus and the nucleo-cytoplasmic shuttling of HuR is generally assumed as the initial and critical step of its stabilizing effects. A number of signaling pathways are believed to be involved in HuR shuttling. Due to the pivotal role played by HuR in stabilizing the mRNA of key factors or cytokines involved in carcinogenesis and subsequent progression, its implication and therapeutic potential in cancer have been investigated intensively since its discovery in 1996. This review discusses the role of HuR in the stabilization of key mRNAs and it’s the nucleo-cytoplasmic shuttling. The review also covers the current knowledge of HuR’s role in carcinogenesis, particularly its involvement in breast cancer, and the feasibility of using HuR as a therapeutic target for the treatment of breast cancer.
- PublicationOpen AccessThe role of neurotrophins related to stress in saliva and salivary glands(Murcia : F. Hernández, 2010) Saruta, Juri; Sato, Sadao; Tsukinoki, KeiichiNerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) are well-studied neurotrophins involved in neurogenesis, differentiation, growth, and maintenance of selected peripheral and central populations of neuronal cells during development and adulthood. Neurotrophins, in concert with the hypothalamic-pituitary-adrenal (HPA) axis, play key roles in modulating brain plasticity and behavioral coping, especially during ontogenetic critical periods, when the developing brain is particularly sensitive to external stimuli. Early life events, such as psychophysical stress, affect NGF and BDNF levels and induce dysregulation of the HPA axis, thereby affecting brain development and contributing to inter-individual differences in vulnerability to stress or psychiatric disorders. Immobilization stress modifies BDNF mRNA expression in some organs. We studied the effect of immobilization stress on BDNF and its receptor tyrosine receptor kinase B (TrkB) in rat submandibular glands, and found increased BDNF expression in duct cells under immobilization stress. Upon further investigation on the influence of salivary glands on plasma BDNF using an acute immobilization stress model, we found that acute immobilization stress lasting 60 min significantly increases the plasma BDNF level. However, plasma BDNF elevation is markedly suppressed in bilaterally sialoadenectomized rats. This suggests that salivary glands may be the primary source of plasma BDNF under acute immobilization stress. This report reviews the structure of salivary glands, the role of neurotrophins in salivary glands, and the significance of BDNF in saliva and salivary glands, followed by a summary of the evidence that indicates the relationship between immobilization stress and BDNF expression within salivary glands.
- PublicationOpen AccessComparison of the dysadherin and E-cadherin expression in primary lung cancer and metastatic sites(Murcia : F. Hernández, 2010) Mitselou, Antigony; Batistatou, Anna; Nakanishi, Yukihiro; Hirohashi, Setsuo; Vougiouklakis, Theodoros; Charalabopoulos, KonstantinosDysadherin, a cancer associated cell membrane glycoprotein, has been reported to downregulate E-cadherin. Aberrant expression of Ecadherin has been associated with the development of metastases in patients with cancer. Even though the expression of dysadherin and E-cadherin has been studied in primary non-small cell lung carcinoma, little is known about its expression at the distant metastases sites. We investigate by immunohistochemistry the relationship between E-cadherin and dysadherin in 111 cases of primary lung carcinomas (53 squamous cell carcinomas, 21 adenocarcinomas, 13 large cell carcinomas, and 24 small cell carcinomas), and their distant metastases. The intensity, the expression pattern and the percentage of neoplastic cell staining were recorded and the results were correlated with clinicopathological findings of the subjects. Dysadherin immunostain was expressed in 61 (54.95%) of the cases, and increased dysadherin expression was significantly correlated with tumour size (p=0.003), distant metastases (p=0.0034), and metastasis size (p=0.0008). Reduced Ecadherin expression was noted in 46 (41.45%) of the cases, and was correlated with high-grade tumour (p=0.02), infiltrative growth pattern (p=0.042), and advanced stage (p=0.032). Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. In lung carcinomas dysadherin expression seems to reflect tumour aggressiveness and may be considered a positive marker of poor prognosis when considered alone or/and in combination with down-regulation of Ecadherin.
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