The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in the stroma of pre-invasive breast cancer

Behrens, P.; Rothe, Marcus; Wellmann, Axel; Krischler, Jutta; Wernert, Nicolas

doi:10.1002/path.844

Cited by 127 publications

(117 citation statements)

References 45 publications

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“…Proteases carry out balanced degradation of extracellular matrix components facilitating tumour invasion (56,(79)(80)(81)(82). In quantitative light cycler analyses we found that media conditioned by DU-145 cells induced in fibroblasts expression of mmp-1 mRNA in contrast to LNCaP and PC-3 conditioned media.…”

Section: Discussionmentioning

confidence: 99%

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Kaminski

Hahne²,

Haddouti³

et al. 2006

Int J Mol Med

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Abstract.Previous work has shown the importance of tumourstroma interactions for prostate cancer development at the primary site. The aim of the present study was to find out whether evidence can be found for a tumour-stroma crosstalk also between metastatic prostate cancer cell lines and non-prostatic stromal fibroblasts which are encountered by metastatic cells at most sites. We addressed this issue in cell culture systems using 3 metastatic human prostate cancer cell lines (LnCaP, PC-3 and DU-145) on the one hand, and a human fibroblast line (HFF, human foreskin fibroblasts) on the other. We incubated fibroblasts with tumour cell-and tumour cells with fibroblast-conditioned media and evaluated several parameters important for the establishment of metastases such as cell proliferation, migration and expression of matrix degrading proteases. We also determined in the conditioned media the concentrations of several growth factors and cytokines which might be responsible for the observed effects. We found that media conditioned by all 3 metastatic prostate cancer cell lines stimulated fibroblast proliferation which corresponds to fibrous stroma induction in vivo. DU-145 cell conditioned media induced in fibroblasts expression of mmp-1 mRNA known to be important for tumour invasion. ELISA assays revealed that tumour cells secrete bFGF, PDGF and TNF· known to stimulate fibroblast proliferation and/or MMP-1 expression. Cultivation of DU-145 carcinoma cells in fibroblast conditioned medium resulted in an enhanced proliferation and anchorage-independent growth of this cell line in soft agar. Fibroblast conditioned medium also increased migration of PC-3 cells in the wound assay and slightly augmented mmp-1 expression. KGF (able to stimulate proliferation of normal and neoplastic prostate epithelial cells) was secreted by fibroblasts at higher concentrations than by all 3 tumour cell lines. In addition, fibroblasts secreted TNF·, bFGF, PDGF, HGF and also VEGF, the most important factor for tumour vascularization. Our results provide evidence that tumour-stroma interactions do not only exist at the primary site but also between metastatic prostate cancer cell lines and their fibroblastic microenvironment. These interactions, which are mediated through secreted factors, affect several steps of the metastatic cascade including proliferation, anchorage-independent growth, migration and the secretion of matrix-degrading proteases.

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Section: Discussionmentioning

confidence: 99%

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Kaminski

Hahne²,

Haddouti³

et al. 2006

Int J Mol Med

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“…This is suggested by the finding of highly upregulated Ets1 transcripts in stromal tissues surrounding breast carcinoma. 28 In the present study, in addition to primary tumors, we used cell lines of highly enriched malignant epithelial cells. The repressed Ets1 expression in these relatively homogenous cells may represent true molecular change in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Profile of Ets gene expression in human breast carcinoma

Pan

Hu³

et al. 2007

Cancer Biology & Therapy

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Background: Ets genes encode a family of transcription factors that play key roles in cell proliferation, differentiation and apoptosis. Fusions of Ets genes with other targets have been described in Ewing's sarcoma, chronic myelomonocytic leukemia and more recently prostate carcinoma. Ets expression in breast carcinoma has not been comprehensively studied, and is the focus of this study.Methods: RT-Q-PCR was used to determine the expression of Ets genes in a panel of ten common breast cancer cell lines, two immortalized normal breast epithelial cell lines, and one primary culture of human mammary epithelial cells. Ets with altered expression in cancer cell lines were verified in primary breast tumors.Results: Transcripts of 21 of the 27 Ets genes were detected in either normal or cancer cells. Of the 21 detectable genes, 14 were expressed at a similar level in both normal and breast cancer cell lines. Four genes, Ehf, Elf3, Elf5 and Pdef, were expressed at higher levels in breast cancer cells than normal epithelials. Surprisingly, the expression of Elk3, Ets1 and Fli1 was repressed in breast cancer cells. The protein status of Ehf, Elf3, Pdef, Elk3, Ets1 and Fli1, strongly correlated with the transcript data, suggesting that Ets expression is regulated primarily at the transcriptional level. Similarly, Elf3, Pdef and Tel2 were overexpressed, while Elk3, Ets1 and Fli1 were under-expressed in primary breast tumor specimens in comparison with normal mammary tissues.Conclusions: Our study identified a subset of Ets genes with altered expression in breast carcinoma, implicating their roles in mammary tumorigenesis. While the Ets overexpression pattern is useful to uncover recurrent genetic alterations involving Ets genes, the repressed expression of several Ets genes suggests that some Ets proteins may play suppressor roles during breast cancer progression. Our results warrant detailed studies of individual Ets activity during mammary gland neoplasia.

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“…The primers were modified by a nonspecific tail for concatamerization, for example, 5 0 -CCC CAA ACC CCA AAC CCC-3 0 and 5 0 -GGG GTT TGG GGT TTG GGG-3 0 . This modification provides a network of generated cDNAs and avoids their displacement 16 resulting in a high specificity of signals. Slides were incubated at 41C 1 h, followed for 2 h at 371C.…”

Section: Tissuementioning

confidence: 99%

In situ-RT and immunolaser microdissection for mRNA analysis of individual cells isolated from epilepsy-associated glioneuronal tumors

Fassunke

Majores

Ullmann

et al. 2004

Laboratory Investigation

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Analysis of gene transcription patterns in complex tissues with multiple cell types is a major challenge. Examination of cellular subpopulations for molecular expression patterns requires their isolation from other surrounding cells. We performed single-cell mRNA analysis to study gangliogliomas obtained from patients with pharmacoresistant epilepsy (n ¼ 6), in order to characterize CD34 expressing cells found in these tumors. Fresh-frozen biopsy tissue was analyzed by initial in situ-reverse transcription (in situ-RT) with oligonucleotides, subsequent immunohistochemistry (IHC) to identify specific cell types, and laser-capture microdissection (LCM, herein termed immuno-LCM) to obtain antigen-expressing cell subpopulations. Isolated complementary DNAs (cDNAs) were then quantified by real time-polymerase chain reaction (RT-PCR). We found that short-vs long-term incubation time for the IHC step did not adversely affect cDNA abundance obtained by subsequent RT-PCR, either for high-abundance (glyceraldehyde dehydrogenase; GAPDH), medium-abundance (glial fibrillary acidic protein; GFAP), or low abundance (neurofilament; NFM) gene transcripts. We also determined that the cellular specificity of capture was excellent, as determined by lack of contamination between different immuno-LCM cell isolates. We were therefore able to examine the lineage expression markers of isolated CD34-expressing cells. We observed coexpression of CD34 and NFM, suggesting neuronal differentiation of the CD34 expressing cellular elements in gangliogliomas. Expression markers for other cellular types (myelin basic protein for oligodendroglia; GFAP for astrocytes) were negative. Our findings support the hypothesis that gangiogliomas contain neuronal elements with compromised or atypical differentiation. We consider that this in situ-RT/immuno-LCM protocol is of general applicability, whereby virtually any primary antibody can be used to facilitate capture of individual cells in tissue sections for molecular analysis.

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The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in the stroma of pre-invasive breast cancer

Cited by 127 publications

References 45 publications

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Profile of Ets gene expression in human breast carcinoma

In situ-RT and immunolaser microdissection for mRNA analysis of individual cells isolated from epilepsy-associated glioneuronal tumors

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