Merck

Lamin A/C is a risk biomarker in colorectal cancer.

PloS one (2008-08-21)
Naomi D Willis, Thomas R Cox, Syed F Rahman-Casañs, Kim Smits, Stefan A Przyborski, Piet van den Brandt, Manon van Engeland, Matty Weijenberg, Robert G Wilson, Adriaan de Bruïne, Christopher J Hutchison
ABSTRACT

A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a beta-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression. An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin. Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
McCoy 5A培养基, Modified, with sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
McCoy 5A培养基, Modified, with L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
SAFC
McCoy 5A培养基, Modified, with L-glutamine, without sodium bicarbonate, powder, suitable for cell culture