The erbB2 gene expression in gynaecological cancers

Generally, one in three of epithelial ovarian cancers may show amplification of the erbB2 gene (Borrensen, 1992). Five to 68 copies of the gene have been encountered in 14 of carcinoma of the uterine cervix (Mitra et al., 1994). Whether gene amplification and or over-expression of the gene product is related to the stage of the disease is unclear. There does not appear to be any relationship between the biological behaviour of ovarian cancers and their erbB2 expression status (Haldane et al.,...

Neural cell adhesion molecule NCAM in differentiation and cancer

The neural adhesion molecule NCAM and yV-cadherin have been studied intensively for their role in neurite regeneration and neuronal adhesion to other cells. NCAM-mediated cell interactions do not require Ca2+, whereas JV-cadherin is a Ca2+-dependent adhesive protein (see page 103). NCAM, like other CAMs discussed above, also possesses immunoglobulin-like domains (Cunningham et al, 1987). Transfection of cDNAs coding for NCAM into cells which do not express these molecules enhances their...

Regulation of mdm2 by p53

The mdm2 (murine double minute 2) was isolated from transformed mouse 3T3 cells and its expression was associated with high tumorigenic potential (Cahilly-Snyder et al, 1987 Fakharzadeh et al., 1991). This gene has been mapped to chromosome 12ql3. The mdm2 gene is amplified in a number of human malignancies. Multiple transcripts of mdm2 have been detected in breast epithelial cells, with protein products ranging from 54-68 kDa to 90-100 kDa (Gudas et al., 1995a). mdm2 has been shown to bind p53...

P53 protein as a transcription factor

The biochemical basis for p53 function is the ability of the phosphoprotein to regulate transcription by binding to DNA. The region between residues 120 and 290 functions as a specific DNA-binding domain. The consensus nucleotide sequence for p53 binds to DNA is 5'-Pu-Pu-Pu-C-A T-A T-G-Py-Py-Py-3' (El-Deiry et al., 1992 Funk et al, 1992). p53 will enhance transcription of a gene that has a p53 responsive element (Farmer et al., 1992 Zambetti et al., 1992). There are five conserved regions in...

Wnt genes in cell proliferation transformation and tumorigenesis

Cell differentiation and proliferation are integral but mutually exclusive components of growth, development and morphogenesis. The demonstration that wnt gene expression may modulate cellular behaviour by altering cellular adhesion has inevitably raised questions concerning the possible implications of their expression for cell proliferation, neoplastic transformation, invasion and tumorigenesis. As stated before, several wnt genes are expressed in the proliferation and differentiation of...

Dominant metastasisassociated genes

The search for metastasis-associated genes expressing as a dominant trait has proceeded alongside the exploration for suppressor genes, albeit at a torpid pace. The natural candidates were oncogenes, which have been studied extensively as they were identified and cloned. However, there has been no unequivocal demonstration of the involvement of known oncogenes in cancer spread. Differential screening of cDNA libraries of non-malignant and corresponding malignant tumour cell lines has revealed a...

Clonal expansion of tumour cell subpopulations

The diverse phenotypes generated during the expansion of tumours do not continue to proliferate and expand ad infinitum. They are subjected to a process of selective evolution. For instance, they are exposed to external pressures such as those imposed by immunological defence mechanisms, growth factor requirements and the ability of the variants to respond to these. From these selective pressures emerge variants which are better adapted to the ambient growth conditions and display more...

ErbB2 expression in other forms of human cancer

Work is less clearly focused upon other forms of human cancer. There is a study on nasopharyngeal carcinoma where erbB2 expression seemed to relate to both overall as well as disease-free survival (Roychowdhury et al., 1996). Underwood et al. (1995) have found erbB2 amplification in 16 out of 89 patients with recurrent transitional cell carcinoma of the bladder, but found no amplification in non-recurrent or normal bladder tissues. Roughly half of the patients with recurrent disease showed...

Alternative splicing of the p53 gene transcript

Genetic alterations of the p53 gene and its dysfunction as a consequence leads, as the preceding pages have shown to a deregulation of cell proliferation and pathogenesis. Other modes of p53 regulation involving post-transcriptional events such as the alternative splicing of pre-mRNA have been suggested. The generation of splice variants of pre-mRNAs of several genes, including p53, has been known for some years. In rat tissues, in which alternative splicing of the original p53 transcript has...

Cathepsin B in cancer invasion

Cathepsin B has been widely studied with regard to its possible function in cancer invasion and metastasis (see Sloane, 1990 Sloane et al., 1990). The possible importance of this cathepsin was highlighted by the demonstration that the metastatic potential of B16 murine melanomas growing as subcutaneous tumours closely correlated with the levels of the enzyme (Sloane et al., 1981,1982). This correlation was subsequently confirmed in other murine tumours (Keren and LeGrue, 1988 Qian et al.,...

GADD genes and their regulation by p53

Having discussed how p53 influences positive signals for proliferation imparted to the cell by growth factors, it would be appropriate to discuss the role of this suppressor protein in regulating genes which impart growth arrest signals. The GADD (Growth Arrest and DNA Damage inducible) family of genes are induced by DNA damage and are associated with growth suppression. GADD45 has a p53 responsive element in the third intron and p53 obtained from irradiated cells binds this to the p53...

APC and MCC genes in colonic tumours

In familial adenomatous polyposis (FAP) the patients develop numerous benign adenomatous polyps which, if left untreated, progress into carcinomas. The APC gene, which is located on chromosome 5q21 (Bodmer et al., 1987), has been identified as causing FAP. The APC gene and the MCC gene, also present at the same locus, are both believed to act as suppressor genes (Kinzler et al., 1991a,b). Mutations of the APC gene, leading to a loss of its suppressor function, have been implicated in FAP...