Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors)

None
Share this:
Embed*
Cite this:

Diaz-Cano, Salvador J.; Alman, B A; Li, C; Wolfe, H J; Pajerski, M E (2012): Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). figshare.

http://dx.doi.org/10.6084/m9.figshare.97674
Retrieved 22:01, Oct 31, 2014 (GMT)

Description

Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.

Links

Comments (0)

You must be logged in to post comments.

Cite "Filename"

Place your mouse over the citation text to select it

Embed "Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors)"

Place your mouse over the embed code to select and copy it

Claim article

You claim request was sent. I will be handled in the next 24 hours.

Close window

Feedback

We appreciate all your comments, questions, suggestions or gratitude.

Login

The username or password entered are wrong.

Reset password

Your password will be sent to your registered e-mail address.

Create account

I agree to the Terms & Conditions *