Expression of tropomyosin isoforms in benign and malignant human breast lesions

Franzén, Bo; Linder, Stig; Uryu, Kiyoaki; Alaiya, Ayodele; Hirano, Takashi; Kato, Harabumi; Auer, Gert

doi:10.1038/bjc.1996.162

Cited by 81 publications

(68 citation statements)

References 12 publications

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“…Tropomyosin levels were lower in carcinomas than in nonmalignant cells, confirming our previous findings (Franzen et al, 1996). In the material analysed here, the decreases in tropomyosin 2 and 3 were statistically significant, but not that of tropomyosin 1.…”

Section: Resultssupporting

confidence: 91%

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Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Franzén

Linder²,

Alaiya³

et al. 1996

Br J Cancer

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Summary Malignant progression of tumour cells is caused by the accumulation of genetic defects, which when combined will generate a large phenotypic diversity. Simultaneous quantitation of a large number of gene products in tumour cells is desirable, but difficult to achieve. We have here quantitated the levels of a number of abundant polypeptides in human breast carcinoma cells using two-dimensional gel electrophoresis (2-DE; PDQUEST). For this purpose, tumour cells were prepared from the tissue of 17 breast carcinomas. Fibroadenoma tissue was used as reference for benign cells. An increase of the spot density of the PCNA polypeptide was observed in rapidly proliferating tumour cells, confirming the validity of the procedures used. In the set of 24 polypeptide spots with known identity, decreases in cytokeratin and tropomyosin levels were observed. The levels of all cytokeratin forms resolved (CK7, CK8, CK15 and CK18) were significantly lower in carcinomas than in fibroadenomas. The levels of tropomyosin 2 and 3 were lower in carcinomas than in fibroadenomas. In contrast, the levels of some members of the stress protein family (pHSP60, HSP90 and calreticulin) were higher in carcinomas. Furthermore, changes in the expression of lactate dehydrogenase and GT-i, but not in nm23, were observed. We conclude that simultaneous analysis of multiple polypeptides in human carcinomas can be achieved by 2-DE and may be useful in prognostic studies, and that malignant progression of breast carcinomas results in the decreased expression of cytokeratin polypeptides. This phenomenon must be considered in studies where cytokeratins are used as markers to identify the epithelial cell compartment in breast carcinomas.Keywords: two-dimensional gel electrophoresis; human breast tumour; cytokeratin Breast cancer is both biologically and clinically a heterogeneous disease. Although presenting without evidence of disseminating cancer, a proportion of women will die rapidly in metastatic disease. In spite of enormous efforts in breast cancer research, three main problems remain: (1) to objectively and reliably select those premalignant lesions which, if untreated, will progress to invasive malignancy; (2) to objectively and reliably determine the aggressiveness of an individual tumour and (3) to analyse cellular properties which allow highly individualised tumour-specific treatment.Two-dimensional gel electrophoresis (2-DE) is a technique which can be used to obtain qualitative and quantitative information on protein expression in cells. In a recent update of the two-dimensional protein database, 1082 proteins were reported to be identified by name (Celis et al., 1995). Identification is aided by recent progress in microsequencing, including mass spectrophotometry. We have here explored 2-DE to characterise polypeptide profiles in human breast carcinomas. Major polypeptides in the gel profiles were identified (mostly cytoskeletal and stress-related proteins) and quantified. We describe alterations in the expression of some of these poly...

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Section: Resultssupporting

confidence: 91%

“…It was recently suggested that Fos oncoproteins induce deregulation of genes encoding cytoskeleton-associated proteins (Jooss et al, 1995). We have previously observed down-regulation of tropomyosin 1-3 in breast carcinoma tissue (Franzen et al, 1996). In the present study, significant down-regulation was observed for tropomyosin 2 and 3.…”

Section: Discussionsupporting

confidence: 68%

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Franzén

Linder²,

Alaiya³

et al. 1996

Br J Cancer

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“…Similar to our findings, low expression of TM1 and TM2 has been detected in cervical carcinoma (Bae et al, 2005), of TM2 in oesophageal squamous cell carcinoma (Jazii et al, 2006) and of TM1 in breast carcinoma (Franzen et al, 1996;Raval et al, 2003). However, higher levels were found in primary breast cancer that had metastasised to the axillary lymph nodes (Franzen et al, 1996).…”

Section: Cytoskeletal Proteinssupporting

confidence: 78%

Differential tissue-specific protein markers of vaginal carcinoma

et al. 2009

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The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin -proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.

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“…Clearly, literature has documented evidence of elevated expression of thymosin b4 (a G-actin-sequestering protein that inhibits actin polymerisation) and loss of tropomyosin (an F-actin-stabilizing protein) correlating with increased aggressiveness of carcinoma cells (Franzen et al, 1996;Kobayashi et al, 2002;Wang et al, 2004). In fast migrating tumour cells, a moderate decrease in cellular F-actin level can potentially enhance cell motility by either increasing the availability of G-actin for actintreadmilling, and/or decreasing the overall rigidity of cell cortex (enhances membrane deformability).…”

Section: Discussionmentioning

confidence: 99%

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

et al. 2007

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Expression of profilin-1 (Pfn1) is downregulated in breast cancer cells, the functional significance of which is yet to be understood. To address this question, in this study we evaluated how perturbing Pfn1 affects motility and invasion of breast cancer cells. We show that loss of Pfn1 expression leads to enhanced motility and matrigel invasiveness of MDA-MB-231 breast cancer cells. Interestingly, silencing Pfn1 expression is associated with downregulation of both cell -cell and cell -matrix adhesions with concomitant increase in motility and dramatic scattering of normal human mammary epithelial cells. Thus, these data for the first time suggest that loss of Pfn1 expression may have significance in breast cancer progression. Consistent with these findings, even a moderate overexpression of Pfn1 induces actin stress-fibres, upregulates focal adhesion, and dramatically inhibits motility and matrigel invasiveness of MDA-MB-231 cells. Using mutants of Pfn1 that are defective in binding to either actin or proline-rich ligands, we further show that overexpressed Pfn1 must have a functional actin-binding site to suppress cell motility. Finally, animal experiments reveal that overexpression of Pfn1 suppresses orthotopic tumorigenicity and micro-metastasis of MDA-MB-231 cells in nude mice. These data imply that perturbing Pfn1 could be a good molecular strategy to limit the aggressiveness of breast cancer cells.

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Expression of tropomyosin isoforms in benign and malignant human breast lesions

Cited by 81 publications

References 12 publications

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Differential tissue-specific protein markers of vaginal carcinoma

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

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