Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization

Tsukamoto, Tetsuya; Mizoshita, Tsutomu; Tatematsu, Masae

doi:10.1007/s10120-006-0375-6

Cited by 47 publications

(56 citation statements)

References 79 publications

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“…In humans, two metaplasias are associated with the precancerous stomach, IM and SPEM (60). Analysis of our Bmpr1a ⌬GEC mice revealed no expression of intestinal markers such as Cdx2, Muc2, or cryptidin often associated with IM (53,54,56). SPEM is observed through transdifferentiation of mature zymogenic cells into SPEM cells following parietal cell loss (40,60).…”

Section: Discussionmentioning

confidence: 87%

“…Alcian bluepositive cells can be found in deep glandular cells that are also positive for TFF2 and Muc6 (12). In light of this and to avoid false positives, RT-PCR was performed to investigate for the presence of Muc2, a specific goblet cell marker, and other classical markers associated with intestinal metaplasia such as Cdx2 and cryptidin (53,54,56). No expression of any of these markers was detected in either Bmpr1a ⌬GEC or control mice (Fig.…”

Section: Loss Of Gastric Epithelial Bmpr1a Leads To a Decrease In Thementioning

confidence: 99%

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Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Maloum

Allaire²,

Gagné‐Sansfaçon³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Perreault N. Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells. Am J Physiol Gastrointest Liver Physiol 300: G1065-G1079, 2011. First published March 17, 2011 doi:10.1152/ajpgi.00176.2010.-Bone morphogenetic protein (BMP) signaling within the gastrointestinal tract is complex. BMP ligands and their receptors are expressed in both epithelial and mesenchymal compartments, suggesting bidirectional signaling between these two entities. Despite an increasing interest in BMP signaling in gut physiology and pathologies, the distinct contribution of BMP signaling in the epithelium vs. the mesenchyme in gastrointestinal homeostasis remains to be established. We aimed to investigate the role of epithelial BMP signaling in gastric organogenesis, gland morphogenesis, and maintenance of epithelial cell functions. Using the Cre/loxP system, we generated a mouse model with an early deletion during development of BMP receptor 1A (Bmpr1a) exclusively in the foregut endoderm. Bmpr1a⌬GEC mice showed no severe abnormalities in gastric organogenesis, gland epithelial proliferation, or morphogenesis, suggesting only a minor role for epithelial BMP signaling in these processes. However, early loss of BMP signaling in foregut endoderm did impact on gastric patterning, leading to an anteriorization of the stomach. In addition, numbers of parietal cells were reduced in Bmpr1a ⌬GEC mice. Epithelial BMP deletion significantly increased the numbers of chromogranin A-, ghrelin-, somatostatin-, gastrin-, and serotonin-expressing gastric endocrine cells. Cancer never developed in young adult (Ͻ100 days) Bmpr1a-inactivated mice although a marker of spasmolytic polypeptide-expressing metaplasia was upregulated. Using this model, we have uncovered that BMP signaling negatively regulates the proliferation and commitment of endocrine precursor cells. Our data also indicate that loss of BMP signaling in epithelial gastric cells alone is not sufficient to induce gastric neoplasia. bone morphogenetic protein; gastric cell lineages; spasmolytic polypeptide-expressing metaplasia

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Section: Discussionmentioning

confidence: 87%

Section: Loss Of Gastric Epithelial Bmpr1a Leads To a Decrease In Thementioning

confidence: 99%

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Maloum

Allaire²,

Gagné‐Sansfaçon³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…[29][30][31][32][33][34][35][36][37][38][39][40][41]60 Its role in carcinogenesis is poorly understood, although deregulation of homeobox gene expression has been implicated in the determining phenotypic expression of gastric, ampullar and pancreatic neoplastic cells and in the biology of cancers arising in these anatomical sites. [61][62][63][64][65][66][67] Furthermore, expression analysis studies have shown that SOX2 is one of the genes differentially expressed between embryonal carcinomas and seminomas. Previous studies 39 have suggested that neoplastic cells of seminomas have phenotypic characteristics similar to those of undifferentiated germ cells, whereas embryonal carcinoma cells resemble pluripotent embryonic stem cells, which have the ability to differentiate.…”

Section: Discussionmentioning

confidence: 99%

Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer

et al. 2007

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Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2 þ tumours, Po0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P ¼ 0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P ¼ 0.022, 0.005 and o0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics. Modern Pathology (2007) 20, 474-481.

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“…or it is just the result in H. pylori-infected gastric carcinoma. Since Shh in the normal gastric gland morphogenesis is a candidate of polarizing signal in the maintenance of gastric pit-gland asymmetry [38] and gastric epithelial renewal is an asymmetric process because a stem cell located halfway up the tubular unit gives rise to both basal gland region and luminal pit compartment [39,40], H. pylori infection leads to compartmental imbalance presenting with proliferative and apoptotic activities. Therefore, we can assume that the Shh producing cell clones appearing after longstanding H .pylori infection behave like ''cancer stem cells", based on the features like proliferative capacity, apparent self renewal, and resistance to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis: Implication for gastric carcinogenesis

Lee¹,

Lee²,

Jung³

et al. 2010

Cancer Letters

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Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization

Cited by 47 publications

References 79 publications

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer

Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis: Implication for gastric carcinogenesis

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