Thymosin β4 Is a Determinant of the Transformed Phenotype and Invasiveness of <i>S</i>-Adenosylmethionine Decarboxylase–Transfected Fibroblasts

Nummela, Pirjo; Yin, Miao; Kielosto, Mari; Leaner, Virna D.; Birrer, Michael J.; Hölttä, Erkki

doi:10.1158/0008-5472.can-05-2421

Cited by 27 publications

(30 citation statements)

References 57 publications

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“…2 Not all of these gene expression changes may, however, be directly involved in transformation, but represent secondary responses to transformation. To identify the genes truly relevant to transformation and to investigate the functional roles of c-Jun in transformation and invasion, we generated tetracycline-regulatable TAM67 transfectants from the AdoMetDCoverexpressing cells (Amdc-pLRT-TAM67).…”

Section: Resultsmentioning

confidence: 99%

“…2 Shortly, the purified RNAs were reverse transcribed with Cy3-and Cy5-endlabeled random 9-mers to generate fluorescent single-stranded cDNA probes, which were then competitively hybridized to the arrays. The analyses were repeated twice with two independent cultures of cells (induced for 6 days) and the mean values are shown.…”

Section: Cdna Microarray Analysesmentioning

confidence: 99%

“…2 Biotinylated cRNA targets were then generated from the RNAs and hybridized to Affymetrix MOE430 Set arrays (Santa Clara, CA; >30,000 genes) as previously described. 2,22,23 Reverse transcription-PCR analysis…”

Section: Oligonucleotide Microarray Analysesmentioning

confidence: 99%

“…One lg of polyadenylated RNA was reverse transcribed to cDNA, and 1:10 (v/v) aliquots of the cRNAs were subjected to PCR amplification using the primers (Proligo, Paris, France) and PCR conditions listed in Supporting Information Table I. Primers and PCR variables for Gapdh, used as a control, were the same as previously described. 2 The reaction products were resolved in 2% agarose gel and the gel was stained with GelStar Nucleic Acid Gel Stain (Cambrex Bio Science Rockland, Rockland, ME). The bands were visualized under UV light and documented with Gel Doc 2000 and Quantity One 4.2.3 software (BioRad, Hercules, CA).…”

Section: Oligonucleotide Microarray Analysesmentioning

confidence: 99%

“…These are the genes downregulated most in AdoMetDC-transformed NIH3T3 cells expressing a tetracycline-inducible TAM67 vector (AmdcpLRT-TAM67 cells; induction for 3 and 6 days), that were previously found to be upregulated in the parental Amdc cells as compared with normal NIH3T3 fibroblasts (for direct comparison, the folds of increase of the respective genes in Amdc cells are 3.2, 3.1, 5.1, 8.3, 2.7, 23.5, 2.4, 6.8, 4.1, 2.2, 3.8, 12.1, 7.3, and 2.3, respectively, as analyzed with Incyte Genomics' arrays). 2 Gene annotations have been updated by BLAST searches of nonredundant databases at the National Center for Biotechnology Information. 1 Note that the value for integrin b7 is compressed due to low performance probe set (specific/nonspecific binding) and those for thymosin b4 and cathepsin L due to high signal levels (saturation).…”

Section: Western Blottingmentioning

confidence: 99%

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Identification of integrins α6 and β7 as c‐Jun‐ and transformation‐relevant genes in highly invasive fibrosarcoma cells

Kielosto

Nummela

Järvinen

et al. 2009

Intl Journal of Cancer

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Understanding the mechanisms of tumor cell invasion is essential for our attempts to prevent cancer deaths. We screened by DNA microarrays the c-Jun-and transformation-related gene expression changes in S-adenosylmethionine decarboxylase (AdoMetDC)-overexpressing mouse fibroblasts that are highly invasive in vivo, and their derivatives expressing a tetracycline-inducible dominant-negative mutant of c-Jun (TAM67) or c-Jun shRNA. Among the small set of target genes detected were integrins a6 and b7, cathepsin L and thymosin b4, all upregulated in the AdoMetDC-transformed cells and downregulated upon reversal of transformation by TAM67 or c-Jun shRNA. The upregulation of integrin a6 subunit, pairing with integrin b1, endowed the transformed cells with the capability to attach to basement membrane laminin and to spread. Further, inhibition of integrin a6 or b1 function with neutralizing antibodies blocked the invasiveness of AdoMetDC-transformants and human HT-1080 fibrosarcoma cells in three-dimensional Matrigel. Moreover, immunohistochemical analyses showed strong integrin a6 staining in high-grade human fibrosarcomas. Our data show that c-Jun can regulate all three key steps of invasion: cell adhesion (integrin a6), basement membrane/extracellular matrix degradation (cathepsin L) and cell migration (thymosin b4). In addition, this is the first study to associate integrin b7, known as a leukocyte-specific integrin binding to endothelial/epithelial cell adhesion molecules, with the transformed phenotype in cells of nonleukocyte origin. As tumor cell invasion is a prerequisite for metastasis, the observed critical role of integrin a6b1 in fibrosarcoma cell invasion/spreading allures testing antagonists to integrin a6b1, alone or combined with inhibitors of cathepsin L and thymosin b4, as chemotherapeutic agents. ' 2009 UICC

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Section: Resultsmentioning

confidence: 99%

Section: Cdna Microarray Analysesmentioning

confidence: 99%

Section: Oligonucleotide Microarray Analysesmentioning

confidence: 99%

Section: Oligonucleotide Microarray Analysesmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

See 3 more Smart Citations

Identification of integrins α6 and β7 as c‐Jun‐ and transformation‐relevant genes in highly invasive fibrosarcoma cells

Kielosto

Nummela

Järvinen

et al. 2009

Intl Journal of Cancer

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Harmless glucose‐modified ruthenium complexes suppressing cell migration of highly invasive cancer cell lines

Lamač

Horáček

Šťastná

et al. 2019

Applied Organom Chemis

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Glucose‐substituted ruthenium complexes [(η6‐benzyl‐glucose)RuCp*]+Cl−, where Cp* = η5‐C5Me5; benzyl‐glucose = peracetylated benzyl β‐d‐glucopyranoside (1), benzyl β‐d‐glucopyranoside (2), have been prepared and used as efficient antimigration and anti‐invasive agents against metastatic breast cancer cells (MDA‐MB‐231) and cisplatin‐resistant ovarian cancer cells (SK‐OV‐3). In addition, these complexes were found to be essentially non‐toxic against non‐cancerous human kidney cells (HEK293).

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Switch to an invasive growth phase in melanoma is associated with tenascin‐C, fibronectin, and procollagen‐I forming specific channel structures for invasion

Kääriäinen¹,

Nummela²,

Soikkeli³

et al. 2006

The Journal of Pathology

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Malignant melanomas are characterized by their high propensity to invade and metastasize, but the molecular mechanisms of these traits have remained elusive. Our DNA microarray analyses of benign nevi and melanoma tissue specimens revealed that the genes encoding extracellular matrix proteins tenascin-C (TN-C), fibronectin (FN), and procollagen-I (PCOL-I) are highly upregulated in invasive and metastatic melanomas. The expression and distribution of these proteins were further studied by immunohistochemistry in benign nevi, radially and vertically growing melanomas, sentinel node micrometastases, and macrometastases. TN-C was increased in all invasive tumours and metastases, especially at invasion fronts, but not in benign nevi or non-invasive melanomas. Significantly, the intensity of TN-C staining correlated with metastasis to sentinel lymph nodes, better than tumour thickness (Breslow). Moreover, TN-C, FN, and PCOL-I appeared to co-localize in the tumours and form tubular meshworks and channels ensheathing the melanoma cells. Our data suggest that melanoma invasion is associated with the formation of special channel-like structures, providing a new concept, structured tumour cell spreading. Altogether, these data provide potential new prognostic markers and therapeutic targets/strategies for preventing melanoma dissemination.

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Thymosin β4 Is a Determinant of the Transformed Phenotype and Invasiveness of S-Adenosylmethionine Decarboxylase–Transfected Fibroblasts

Cited by 27 publications

References 57 publications

Identification of integrins α6 and β7 as c‐Jun‐ and transformation‐relevant genes in highly invasive fibrosarcoma cells

Identification of integrins α6 and β7 as c‐Jun‐ and transformation‐relevant genes in highly invasive fibrosarcoma cells

Harmless glucose‐modified ruthenium complexes suppressing cell migration of highly invasive cancer cell lines

Switch to an invasive growth phase in melanoma is associated with tenascin‐C, fibronectin, and procollagen‐I forming specific channel structures for invasion

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