Identification of genes involved in epithelial-mesenchymal transition and tumor progression

Abstract

The adenovirus E1A12S gene product (WT12S) immortalizes epithelial cells and they retain their dierentiated characteristics, but certain mutants cannot do the latter. Characterization of mutant immortalized epithelial cells indicated that they had undergone epithelial mesenchymal transition (EMT). Coexpression of V12ras with WT12S leads to benign tumors, but to malignant tumors with 12S mutants. Since EMT is critical for tumor progression, identi®cation of the molecular mechanisms involved should elucidate novel therapeutic targets. To this end, representational dierence analysis (RDA) was used to identify cDNAs upregulated in the mutant cell line. Thirty-®ve dierentially expressed mRNAs were identi®ed and classi®ed into several functional categories, including nine novel cDNAs. Among the 26 known cDNAs, extracellular matrix and related proteins made up the largest group of dierentially expressed genes, followed by growth factors and receptors and transcription factors. There was also an ion transporter, a cytoskeletal protein, glycosylation and amidinotransferase enzymes and proteins with unknown functions. Some of the known genes have previously been associated with EMT and/or tumor progression and thus served to validate the system to obtain the desired target genes, while other cDNAs are newly linked with dedierentiation/malignancy. Array analyses indicated that the cDNAs were speci®cally upregulated in invasive or metastatic tumors, especially of breast, uterus and lung, suggesting their involvement in the progression of these tumors. Oncogene (2001) 20, 6679 ± 6688.

Cyclooxygenase‐2 overexpression in MCF‐10F human breast epithelial cells inhibits proliferation, apoptosis and differentiation, and causes partial transformation

“…These findings suggest that 10F-S cells were undergoing epithelial to mesenchymal transition (EMT), a process that characterizes progression towards a malignant phenotype. 43,44 The 10F-S cells, however, were unable to grow in soft agar and did not form tumors in nude mice showing that they are not fully transformed. We have now cultured the 10F-S cells for an additional 10 passages and observed no further changes.…”

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

“…As a consequence, studies have to rely on comparing different expression levels of Ep-CAM, the accuracy of which is limited by the semiquantitative nature of immunohistochemical staining procedures. A hallmark of tumour cells is de-differentiation, which typically goes along with the loss of expression of differentiation markers (Kiemer et al, 2001;Peinado et al, 2004). Epithelial cell adhesion molecule is an epithelial differentiation marker, which is frequently expressed on normal epithelial cells (Winter et al, 2003).…”

Bone morphogenetic protein 3B silencing in non-small-cell lung cancer

“…In all, 10 mice were used for pBabe and pBabe-BMP3B groups, respectively BMP3B in non-small-cell lung cancer Z Dai et al been postulated that fibronectin promotes migration of cancer cells, an important step in epithelial to mesenchymal transition (Ridley, 2000). In addition, fibronectin is upregulated during adenovirus E1A 12S mutant HBdl12-induced epithelial to mesenchymal transition in primary kidney cells (Kiemer et al, 2001). TGFBI is a gene that was originally identified by differential hybridization as a target of TGF-b that could be induced up to 20-fold after 2 days of TGF-b treatment in A549 cells (Skonier et al, 1992).…”