When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin), a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What can this pathway teach us about translating basic science into clinical use?

/pdf/untangling-the-erbb-signalling-network-1b92otnrud.pdf

Untangling the ErbB signalling network

https://www.cell.com/cell/pdf/0092-8674(92)90123-T.pdf

Induction of apoptosis in fibroblasts by c-myc protein

https://www.cell.com/cell/pdf/0092-8674(91)90642-C.pdf

Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation.

Epidermal growth factor-related peptides and their receptors in human malignancies

Structure, Recognition, and Processing of Cisplatin-DNA Adducts.

Advances in the field of oncogenes have produced a tool to investigate the different stages in multistep carcinogenesis. The role of the ras and myc gene families have been extensively investigated in the progression of carcinogenesis in a range of human solid tumours. This review critically analyses the data available on the role of these oncogenes in the six most common cancers worldwide, (i.e. cancer of the stomach, lung, breast, colon, cervix, and mouth and pharynx). In certain cases the incidence of aberrant gene expression and genetic alterations of the ras and myc gene families have been shown to be important in the progression of these cancers and may be of use as prognostic indicators.

The role of ras and myc oncogenes in human solid tumours and their relevance in diagnosis and prognosis (review).

Expression of six cellular oncogenes in fresh human tumours and normal tissue from head and neck regions of 20 patients were assessed: 7 samples of normal tissue (controls), 4 premalignant (pleomorphic salivary adenoma) and 14 malignant tumours (squamous cell carcinoma) were examined. Normal and malignant tissue was available from the same patient in four cases, whereas normal and premalignant tissue in one case. Significant elevation of Ha-ras, Ki-ras, and myc oncogene expression were found both in premalignant and malignant tumours as compared to the normal tissue. Oncogenes fes, abl, and sis were expressed at similar low levels in all tissues examined. The results suggest activation of multiple oncogenes in premalignant and malignant tumours from the human head and neck regions.

Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours.

Immunohistochemical study of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) expression was performed on paraffin-embedded tissue specimens of 70 squamous cell lung carcinomas. The carcinomas were placed to one of the following eight groups, according to the results of EGF, TGF-alpha and EGFR expression: group 1: none, group 2: only EGFR, group 3: EGFR and TGF-alpha, group 4: EGFR and EGF, group 5: TGF-alpha and EGF, group 6: all three, group 7: only TGF-alpha and finally group 8: only EGF. Statistical analysis of the results revealed that the ratio of squamous cell lung carcinomas with lymph node metastasis was significantly higher in groups 4, 5 and 6 (P less than 0.01). We also examined whether EGF receptors were truncated with the use of two monoclonal antibodies directed against different portions of the receptor (EGFR1 and F4). No truncated EGF receptors were detected. These results suggest that lung carcinomas expressing the molecules EGF/EGFR, TFG-alpha/EGFR or TGF/alpha/EGF/EGFR display pathologic features of more aggressive disease.

Expression of EGF, TGF-alpha and EGFR in squamous cell lung carcinomas.

http://helios-eie.ekt.gr/EIE/bitstream/10442/7332/2/Zoumpourlis_IJ_15.pdf

p53 expression and mutations in squamous cell carcinoma of the head and neck: expression correlates with the patients' use of tobacco and alcohol.

The expression of ras, c-myc and c-erbB-2 oncoproteins in 100 human (73 ductal and 27 lobular) breast carcinomas has been examined using an immunohistochemical analysis. The monoclonal antibody Y13 259 has been used for the ras p21, the monoclonal antibody Myc1-9E10 for the c-myc p62 and the polyclonal antibody pAb1 (from Triton Bioscience Inc.) for the c-erbB-2 p185 oncoproteins. The following conclusions can be drawn from the analysis: Of the 100 breast carcinoma cases studied only 14 did not express any of the three oncogenes. The remaining 86 were positive for one or more of the three oncoproteins. Ductal carcinomas expressed oncoproteins in 92% of the cases (67/73), whereas lobular carcinomas expressed them in 70% of the cases (19/27). The most frequently expressed was c-myc p62 in 70% of cases followed by ras p21, 55% and c-erbB-2, 35%. Elevated expression of ras, myc or erbB-2 oncogenes did not correlate with the presence of metastasis in auxiliary lymph nodes, the numbers of infiltrated lymph nodes the grade of the tumor or hormone status. However, there appears to be a correlation between increased ras staining intensity and patient's age, below 50 years.

Da Spandidos

Papers

The role of ras and myc oncogenes in human solid tumours and their relevance in diagnosis and prognosis (review).

Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours.

Expression of EGF, TGF-alpha and EGFR in squamous cell lung carcinomas.

p53 expression and mutations in squamous cell carcinoma of the head and neck: expression correlates with the patients' use of tobacco and alcohol.

ras, c-myc and c-erbB-2 oncoproteins in human breast cancer.