SOX2 in gastric carcinoma, but not Hath1, is related to patients' clinicopathological features and prognosis.
ABSTRACT SOX2 and Hath1 are transcription factors that are critical for the control of terminal cell differentiation in the gastrointestinal mucosa. This study investigated the correlations between SOX2 and Hath1 expression in gastric carcinoma and patients' clinicopathological features and prognosis.
Hath1 and SOX2 were detected by immunohistochemistry in gastric carcinoma (n = 50). Probability of survival of patients after surgery was estimated by the Kaplan-Meier method and compared using Log-rank test.
Hath1 and SOX2 were inversely expressed in gastric carcinoma. Patients with strong SOX2 expression (++ to +++) showed lower incidences of lymph node metastasis (p = 0.007), deeper invasion (p = 0.010), and III-IV clinical stages (p = 0.011) compared to patients with low SOX2 expression (- to +). There was no significant difference in SOX2 and Hath1 expression in the cancerous tissues of the patients with and without Helicobacter pylori infection (p > 0.05). The patients with strong expression of SOX2 in their cancerous tissues (++ to +++) had a better prognosis than those with low expression of SOX2 (- to +; p = 0.005). There was no correlation between Hath1 expression level and prognosis (p = 0.676).
SOX2 and Hath1 are inversely expressed in gastric carcinoma. SOX2 provides a survival advantage to patients of gastric carcinoma and appears to be associated with metastasis and clinical stages.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: Mice lacking the proneural transcription factor Math1 (Atoh1) lack multiple neurons of the proprioceptive and arousal systems and die shortly after birth from an apparent inability to initiate respiration. We sought to determine whether Math1 was necessary for the development of hindbrain nuclei involved in respiratory rhythm generation, such as the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), defects in which are associated with congenital central hypoventilation syndrome (CCHS). We generated a Math1-GFP fusion allele to trace the development of Math1-expressing pFRG/RTN and paratrigeminal neurons and found that loss of Math1 did indeed disrupt their migration and differentiation. We also identified Math1-dependent neurons and their projections near the pre-Bötzinger complex, a structure critical for respiratory rhythmogenesis, and found that glutamatergic modulation reestablished a rhythm in the absence of Math1. This study identifies Math1-dependent neurons that are critical for perinatal breathing that may link proprioception and arousal with respiration.Neuron 11/2009; 64(3):341-54. · 15.77 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Other than ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, the molecular mechanisms underlying gastric and intestinal phenotypes of human stomach adenocarcinomas have yet to be clarified in detail. We have reported that Sox2, an HMG-box gastric transcription factor, is expressed in normal gastric mucosa and down-regulated in intestinal metaplasia. We analysed mRNA levels of Sox2 and other differentiation markers in 50 surgically resected stomach adenocarcinomas, immunohistochemically classified into gastric (G), gastric-and-intestinal (GI)-mixed, solely intestinal (I), and null (N) types. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2. A stomach adenocarcinoma cell line, KATOIII, demonstrated both MUC5AC and Sox2, although MUC5AC mRNA was not detected in the Sox2+ AGS cell line. Sox2 may play an important role in maintaining a gastric phenotype in stomach cancers as well as in normal tissue, in cooperation with other cofactor(s).Histopathology 07/2005; 46(6):649-58. · 2.86 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment. Atonal homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix-loop-helix transcription factor required for hair-cell development, and its misexpression in vitro and in vivo generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory and vestibular dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction and show basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness.Nature 09/2008; 455(7212):537-41. · 38.60 Impact Factor