Structure and expression of oncogenes in surgical specimens of human breast carcinomas

Biunno, Ida; Pozzi, Maria Rosa; Pilotti, Silvana; Cattoretti, Giorgio; Porta, Giuseppe Della

doi:10.1038/bjc.1988.108

Cited by 25 publications

(8 citation statements)

References 27 publications

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“…The degree of amplification varied from 8% in some reports (19) to 47% in other reports (5). Slamon et al (1) were the first to report C-erbB-2 amplification in breast carcinoma, which they found in about 30% of the tumors.…”

Section: Discussionmentioning

confidence: 97%

“…Different groups of investigators have found that C-erbB-2 is overexpressed in some primary adenocarcinoma of the breast (1, 3, 5, 11, 13, [19][20][21][22][23][24][25][26][27]. The degree of amplification varied from 8% in some reports (19) to 47% in other reports (5).…”

Section: Discussionmentioning

confidence: 99%

“…During the last years different groups have studied the relation between C-erbB-2 and primary adenocarcinoma of the breast (1,3,5,11,13,(19)(20)(21)(22)(23)(24)(25)(26)(27) but the results are controversial. Most authors have tried to correlate neu oncogene with other prognostic parameters like age, lymph node status, histological grade and receptor status.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Neu (C-erbB-2) Oncogene in Breast Cancer and its Possible Association with the Risk of Distant Metastases a Retrospective Study and Review of Literature

Ap¹,

Ej²,

Cr³

et al. 1990

Acta Oncologica

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neu (C-erbB-2) Oncogene in Breast Cancer and its Possible Association with the Risk of Distant Metastases a Retrospective Study and Review of Literature

Ap¹,

Ej²,

Cr³

et al. 1990

Acta Oncologica

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“…(54). In human breast cancer, c-fos overexpression is associated with malignant progression (55,56). Hypoxia on the other hand is a known inducer of metastasis (57).…”

Section: C-fos Induction By Hypoxia Via Mapkmentioning

confidence: 99%

Hypoxia Induces c-fos Transcription via a Mitogen-activated Protein Kinase-dependent Pathway

Müller¹,

Krauß

Kaltschmidt

et al. 1997

Journal of Biological Chemistry

131

100

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Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. It is characterized by a decrease of reactive oxygen intermediates and a change of the intracellular redox level. In tumors hypoxia is regarded as a trigger for enhanced growth and metastasis. Here we report that in HeLa cells, hypoxic conditions induce the transcriptional activation of c-fos transcription via the serum response element. Mutations in the binding site for the ternary complex factor Elk-1 and the serum response factor abolished this induction, indicating that a ternary complex at the serum response element is necessary for the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was covalently modified by phosphorylation in response to hypoxia. Furthermore this hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase 1. An in vitro kinase assay with Elk-1 as substrate showed that MAPK is activated under hypoxia. The activation of MAPK corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a decrease of the intracellular reactive oxygen intermediate level by hypoxia induces c-fos via the MAPK pathway. These results suggest that the intracellular redox levels may be directly coupled to tumor growth, invasion, and metastasis via Elk-1-dependent induction of c-Fos controlled genes.The activation of c-fos by mitogens and changes of the intracellular redox level is mainly mediated by the serum response element (SRE).1 The SRE is a regulatory element found in many growth factor-regulated promotors that directs the rapid induction of gene expression (for review see Ref. 1). The best studied SRE is that of the c-fos gene. Two kinds of transcription factors are required for SRE activity: the ubiquitous transcription serum response factor (SRF) (2) and the ternary complex factors (TCFs), which form a ternary complex with the SRF. The human TCFs include Elk-1, SAP-1, and SAP-2 and constitute a subfamily within the Ets family of transcription factors (for review see Ref.3). These proteins need SRF to bind tightly to the SRE (4). The N-terminal domains of Elk-1 and SAP-1 mediate DNA contact and ternary complex formation. The transactivation domain at the C terminus contains several conserved MAPK phosphorylation sites. Growth factor-stimulated activation of the MAPK pathway results in phosphorylation of the Elk-1 C terminus (5), which then cooperates with the SRF C-terminal activation domain to activate transcription (6, 7).The transcription factor AP-1 is composed of members of the Fos family (c-Fos, Fos-B, Fra-1, and Fra-2) and the Jun family (c-Jun, JunB, and JunD) that form restricted homo-or heterodimers (for review see Ref. 8). With the exception of c-Jun homodimers, AP-1 is predominantly induced at a transcriptional level by novel synthesis of its subunits. Thi...

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“…In a wide range of human tumors, the c fos proto-oncogene has been found expressed at high levels [15]. In human breast tumors, for example, c fos transcript is most frequently high [16], and the degree of its expression is correlated to its histological grading, with more cells positive for c fos mRNA in advanced lesions [17]. Furthermore, its expression increases in pancreatic carcinomas [18], neuromas, meningiomas [19], melanomas [20] and certain leukemias [21].…”

Section: Discussionmentioning

confidence: 99%

Screening of Specific Changes in mRNAS in Thyroid Tumors by Sequence Specific Differential Display. Decreased Expression of c-fos mRNA in Papillary Carcinoma.

et al. 1999

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Abstract.To examine the specific changes in gene expression in thyroid carcinomas, we performed sequence specific-differential display (SS-DD) analysis by using a specific degenerate primer for the superfamily of the small G protein.After subcloning and sequencing analysis, one of the genes that showed decreased expression in thyroid papillary carcinomas was revealed to be the proto-oncogene c fos.Expression of c fos mRNA in benign and malignant tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. The expression of c fos was detected in all twelve normal thyroid tissues, whereas it decreased in thirteen of fifteen papillary carcinomas.These results indicate that the increased expression of c fos mRNA is not necessarily to be an oncogenic feature of thyroid tumors.Further, its constant expression in normal thyroid tissues may play a role in the maintenance of thyroid function.

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Structure and expression of oncogenes in surgical specimens of human breast carcinomas

Cited by 25 publications

References 27 publications

Neu (C-erbB-2) Oncogene in Breast Cancer and its Possible Association with the Risk of Distant Metastases a Retrospective Study and Review of Literature

Neu (C-erbB-2) Oncogene in Breast Cancer and its Possible Association with the Risk of Distant Metastases a Retrospective Study and Review of Literature

Hypoxia Induces c-fos Transcription via a Mitogen-activated Protein Kinase-dependent Pathway

Screening of Specific Changes in mRNAS in Thyroid Tumors by Sequence Specific Differential Display. Decreased Expression of c-fos mRNA in Papillary Carcinoma.

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