Cyclin D1 protein oscillates and is essential for cell cycle progression in human tumour cell lines.

Among the key cell cycle regulators, cyclin D1 has been implicated most strongly in oncogenesis. This G1 cyclin is a putative proto-oncogene whose clonal rearrangement and/or amplification and mRNA overexpression occurs in several types of human neoplasias. We have now raised a series of monoclonal antibodies to human cyclin D1 and analysed its regulation at the protein level in 40 human tumour cell lines.

Molecular pathology of the cell cycle in human cancer cells.

Recent evidence from molecular biology studies of the cell cycle machinery suggests that, apart from oncogenes and tumor suppressor genes, the genes encoding the key cell cycle regulatory proteins could serve as additional targets for oncogenic mutations involved in the multistep process of carcinogenesis. In an attempt to identify such potential cancer-associated aberrations of the cell cycle regulators, the expression of cdc2 and cdk2 kinases, as well as cyclins A, B1 and D1, was analyzed by immunoblotting in a panel of more than 40 human cancer cell lines derived from 17 different tumor types. The expression of cdc2, cdk2, cyclin B1 and cyclin A polypeptides was detectable in all lines examined, and moderate variation in protein level does not provide evidence for any obvious abnormalities in the cancer cell lines studied.

Immunohistochemical analysis of the p53 oncoprotein on paraffin sections using a series of novel monoclonal antibodies.

Alterations of the p53 tumour suppressor gene are considered critical events in multistage carcinogenesis of a wide range of human cancers. In an attempt to elucidate the role of various p53 mutations in tumorigenesis and to investigate their relationship to the p53 protein accumulation and subcellular localization, we have raised a new series of 21 mouse monoclonal antibodies (MAbs) to human recombinant p53. The new MAbs (designated the Bp53 series) appear to recognize mainly denaturation-resistant epitopes in immunoblotting and the majority of them are suitable for immunostaining of p53 in cultured cells and frozen sections.

[Aberrations of the p53 antioncogene in malignant tumors].

The results of the present study of the p53 antioncogene in a broad panel of human cell lines (n = 32) and biopsy specimens (n = 435) from both normal and tumour tissues can be summarized as follows: 1. Cells in primary cultures from normal tissues express very low levels of the p53 protein while strong nuclear accumulation of p53 can be seen in all SV 40 transformed human cell lines and the vast majority of tumour--derived cell lines studied. 2.

p53 protein alterations in human testicular cancer including pre-invasive intratubular germ-cell neoplasia.

Expression of the p53 oncoprotein was examined in a wide range of primary human testicular germ-cell tumours using a new mouse monoclonal antibody (MAb) BP53-11 raised and characterized in this study, in parallel with a polyclonal rabbit antiserum CM-1. Immunohistochemistry on paraffin sections showed positive nuclear reaction in at least a fraction of malignant cells in 90 (84%) out of 107 cases studied. Aberrant accumulation of the p53 protein was found among testicular tumours of all major histological types, although generally a higher percentage of positive cases and a higher proportion of p53 over-expressing nuclei within individual lesions was observed in embryonal carcinomas when compared with seminomas.