Expression of CD44 in premalignant and malignant Barrett's oesophagus

Lagorce-Pagès, Christine; Paraf, F; Dubois, Sylvie; Belghiti, Jacques; Fléjou, J.-F.

doi:10.1046/j.1365-2559.1998.00316.x

Cited by 31 publications

(19 citation statements)

References 29 publications

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“…However, Hoxb13 mutant mice did not reveal any phenotypes of prostatic intraepithelial neoplasia, which may require the loss of another regulatory protein, such as Nkx3.1. The missexpression of CD44 in luminal epithelial cells observed in these mice is consistent with preneoplastic lesions in many tissue types (29,30).…”

Section: Discussionsupporting

confidence: 75%

HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

Jung¹,

Kim²,

Lee³

et al. 2004

Cancer Research

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In prostate gland, HOXB13 is highly expressed from the embryonic stages to adulthood. However, the function of HOXB13 in normal cell growth and tumorigenesis is not yet known. We investigated the role of HOXB13 and mechanism by which it functions in HOXB13-negative cells. Expression of HOXB13 was forced in HOXB13-negative PC3 prostate cancer cells using a liposome-mediated gene transfer approach. Compared with the control clones, HOXB13-expressing PC3 cells exhibited significant inhibition of in vitro and in vivo cell growth with G 1 cell cycle arrest mediated by the suppression of cyclin D1 expression. Because cyclin D1 is mainly regulated by ␤-catenin/T-cell factor (TCF), TCF-4 response element was used in a reporter gene transcription assay, demonstrating that HOXB13 significantly inhibits TCF-4-mediated transcriptional activity in both prostate and nonprostate cells. This inhibition occurred in a doseresponsive manner and was specific to TCF-4 response element. Western blot analysis demonstrated that HOXB13 down-regulates the expression of TCF-4 and its responsive genes, c-myc and cyclin D1. HOXB13 also suppressed the activity of natural c-myc promoter. This study suggests that HOXB13, a transcription factor, functions as a cell growth suppressor by negatively regulating the expression of TCF-4, which eventually provides negative signals for cell proliferation. This observation will provide valuable insight into the molecular basis of prostate tumorigenesis.

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Section: Discussionsupporting

confidence: 75%

HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

Jung¹,

Kim²,

Lee³

et al. 2004

Cancer Research

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“…Given these data, it is likely that there is a loss of identity and impaired secretory function of cells in the luminal epithelium rather than a complete transformation to a different prostatic lobe. The misexpression of CD44 on the apical surface in luminal cells in the Hoxb13 homozygous mutant ventral prostate is consistent with preneoplastic lesions in many tissue types (Sugar et al, 1997;Lagorce-Pages et al, 1998;Wimmel et al, 2001) and in prostate tumors (Paradis et al, 1998). Interestingly, loss of heterozygosity of the 17q21 locus, which spans the Hoxb cluster, in humans is linked to early events of prostate carcinogenesis such as preneoplastic lesions (Brothman et al, 1995;Brothman, 1997;Deubler et al, 1997).…”

Section: Discussionmentioning

confidence: 74%

Hoxb13is required for normal differentiation and secretory function of the ventral prostate

2003

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The murine prostate is a structure that is made up of four distinct lobes; the dorsal and lateral prostates (often grouped together as the dorsolateral prostate), the anterior (coagulating gland) and the ventral prostate. Previous work has implicated Hox genes in the development of these structures, but how each lobe acquires unique identities for specific functions has not been addressed. In this study, the ventral prostate-specific function of Hoxb13 is described. Mice lacking Hoxb13 function show normal numbers of duct tips, but mice mutant for both Hoxb13 and Hoxd13 exhibit severe hypoplasia of the duct tips, revealing a role for Hoxb13 in ventral prostate morphogenesis. Additionally, a ventral lobe-specific defect was identified in Hoxb13 mutants wherein the epithelium is composed of simple cuboidal cells rather than of tall columnar cells. Ventral prostate ducts appear devoid of contents and do not express the ventral prostate-specific secretory proteins p12, a kazal-type protease inhibitor and p25, a spermine binding protein. These defects are not due to reduction of Nkx3.1 expression or to a global effect on androgen receptor signaling. These results suggest a specific role for Hoxb13 in a differentiation pathway that gives the ventral prostate epithelium a unique identity, as well as a more general role in ventral prostate morphogenesis that is redundant with other Hox13 paralogs.

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“…CD44 standard (CD44s) and its abnormal transcripts (CD44v) have been detected in esophageal adenocarcinoma. [173][174][175] Increased CD44s expression was seen in 50% to 66% of esophageal adenocarcinomas (Dr. K.K. Krishnadath, personal communication, November 1997).…”

Section: Cd44 Protein Familymentioning

confidence: 99%

Molecular Biology of Barrett’s Adenocarcinoma

Wijnhoven

Tilanus²,

Dinjens³

2001

Annals of Surgery

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ObjectiveTo review the current knowledge on the genetic alterations involved in the development and progression of Barrett's esophagus-associated neoplastic lesions. Summary Background DataBarrett's esophagus (BE) is a premalignant condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE predisposes patients to the development of esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal adenocarcinomas when they are early and curable, but most of the adenocarcinomas are detected at an advanced stage. Despite advances in multimodal therapy, the prognosis for invasive esophageal adenocarcinoma is poor. A better understanding of the molecular evolution of the Barrett's metaplasia to dysplasia to adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis. MethodsThe authors reviewed data from the published literature to address what is known about the molecular changes thought to be important in the pathogenesis of BE-associated neoplastic lesions. ResultsThe progression of Barrett's metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. Some of the molecular alterations already showed promise as markers for early cancer detection or prognostication. Among these, alterations in the p53 and p16 genes and cell cycle abnormalities or aneuploidy appear to be the most important and well-characterized molecular changes. However, the exact sequence of events is not known, and probably multiple molecular pathways interact and are involved in the progression of BE to adenocarcinoma. ConclusionsFurther research into the molecular biology of BE-associated adenocarcinoma will enhance our understanding of the genetic events critical for the initiation and progression of Barrett's adenocarcinoma, leading to more effective surveillance and treatment.Since 1970, the incidence of adenocarcinomas of the esophagus has increased in many countries at a rate that exceeds that of any other malignancy.

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Expression of CD44 in premalignant and malignant Barrett's oesophagus

Cited by 31 publications

References 29 publications

HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

Hoxb13is required for normal differentiation and secretory function of the ventral prostate

Molecular Biology of Barrett’s Adenocarcinoma

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