Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation

Saldanha, Gerald; Ghura, V.; Potter, Linda; Fletcher, A.

doi:10.1111/j.1365-2133.2004.06048.x

Cited by 108 publications

(102 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nuclear b-catenin is increased in human BCCs (El Bahrawy et al, 2003;Saldanha et al, 2004). We stained sections of BCC-like lesions induced by tet on Gli1 (Li et al, 2006) using an antibody to the active, unphosphorylated form of b-catenin.…”

Section: Gli1 Induces the Accumulation Of Transcriptionally Active B-mentioning

confidence: 99%

“…In Xenopus animal caps, induction of Wnt8 and Wnt11 is important for Gli2-mediated alteration of the posterior mesoderm (Mullor et al, 2001). Human BCCs have constitutive Shh pathway signaling and show increased levels of Wnt2b and Wnt5a and increased levels of nuclear b-catenin (Bonifas et al, 2001;El Bahrawy et al, 2003;Saldanha et al, 2004;Hooper and Scott, 2005). As observed for Shh pathway genes such as Gli1, b-catenin promotes follicle-like tumors or BCCs in transgenic mice (Alonso and Fuchs, 2003;Nicolas et al, 2003).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Gli1 acts through Snail and E-cadherin to promote nuclear signaling by β-catenin

et al. 2007

View full text Add to dashboard Cite

Section: Gli1 Induces the Accumulation Of Transcriptionally Active B-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Gli1 acts through Snail and E-cadherin to promote nuclear signaling by β-catenin

et al. 2007

View full text Add to dashboard Cite

“…Specifically, efforts have been focused on the incidence of nuclear accumulation of b-catenin, a hallmark of constitutive activation of Wnt signalling, in BCC tumor samples (Behrens et al, 1996;Huber et al, 1996). However, several such attempts to detect nuclear accumulation of b-catenin have yielded conflicting observations (Boonchai et al, 2000;Yamazaki et al, 2001;El-Bahrawy et al, 2003;Saldanha et al, 2004). To further verify the involvement of Wnt pathway in BCC, we constructed a tissue microarray (TMA) of 75 BCC tumors and corresponding normal skin samples, and analysed these samples for b-catenin expression and Figure 1f).…”

mentioning

confidence: 99%

“…However, several subsequent studies using different antibodies were able to detect nuclear bcatenin in 23-70% of BCC samples (Yamazaki et al, 2001;El-Bahrawy et al, 2003;Saldanha et al, 2004). Although the precise reasons for such discrepancies is not clear, it has been suggested that this could be caused by differences in tissue fixation and processing (Yamazaki et al, 2001;Saldanha et al, 2004).…”

mentioning

confidence: 99%

RUNX3 protein is overexpressed in human basal cell carcinomas

et al. 2006

View full text Add to dashboard Cite

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of b-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/ transforming growth factor-b pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of b-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

show abstract

“…In addition, CTNNB1 mutations are associated with specific cancers. 15,16 Infection data from in vitro and in vivo experiments demonstrated that CTNNB1 shRNA-expressing SL could not only induce potent and specific gene silencing of CTNNB1, c-Myc and cyclin D1, but also promote tumor and polyp regression. Moreover, efficient silencing of CTNNB1 was also obtained in mucosal tissues from APC Min mice after oral administration of SL-pSLS-mCAT.…”

Section: Introductionmentioning

confidence: 99%

Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi

2010

View full text Add to dashboard Cite

RNA interference (RNAi) has been established as an important research tool that carries great potential for gene therapy. However, targeted induction of RNAi in vivo has met with significant challenges. In this study, a novel pSLS plasmid capable of expressing short hairpin RNAs (shRNAs) was transformed into attenuated Salmonella enterica serovar typhimurium strain 7207 (SL). In vitro infection studies with the transformed S. enterica containing pSLS (SL-pSLS-CAT) demonstrated that expression of shRNA targeting the CTNNB1 gene induced potent and specific silencing of CTNNB1 expression in cultured SW480 cells. CTNNB1 knockdown in SW480 cells was associated with markedly reduced proliferation and cell death compared with that of control infected cells. In addition, SL-pSLS-CAT-mediated CTNNB1 knockdown markedly reduced tumor growth in SW480 xenograft mice. These tumors exhibited reduced levels of CTNNB1, as well as c-Myc and cyclin D1. Finally, SL-pSLS-CAT treatment also resulted in reduced expression levels of these genes in polyps, mucosal tissues and in small intestines of APC Min mice. Taken together, these data suggest that attenuated shRNA-expressing Salmonella may be a powerful new tool for in vitro gene silencing, functional genomics, and the development of RNAi-based anticancer or human immunodeficiency virus therapeutics.

show abstract

Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation

Cited by 108 publications

References 25 publications

Gli1 acts through Snail and E-cadherin to promote nuclear signaling by β-catenin

Gli1 acts through Snail and E-cadherin to promote nuclear signaling by β-catenin

RUNX3 protein is overexpressed in human basal cell carcinomas

Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi

Contact Info

Product

Resources

About