The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts.

The E8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide which contributes to cell transformation by conferring anchorage-independent growth. Using an in vitro translation system, we show that the E8 polypeptide binds to ductin, the 16-kDa proteolipid that forms transmembrane channels in both gap junctions and vacuolar H+-ATPase. This association is not due to nonspecific hydrophobic interactions. PPA1, a Saccharomyces cerevisiae polypeptide homologous (with 25% identity) to ductin, does not complex with E8. Furthermore, E5B, structurally similar to E8 but with no transforming activity, does not form a complex with ductin. Primary bovine fibroblasts expressing E8 show a loss of gap junctional intercellular communication, and it is suggested that this results from the interaction between E8 and ductin.

An ultrastructural evaluation of cell heterogeneity in invasive ductal carcinomas of the human breast. I. An in vivo study.

The present ultrastructural study has been undertaken in order to contribute to the problem of morphological heterogeneity in the ductal infiltrating carcinoma of the human breast. In spite of the well known topographical variability of scirrhous breast cancers, the comparative analysis of 12 primary tumours has brought to light some basic phenotypical expressions of the neoplastic cell population. The major observation is the occurrence of two main categories of cells, which are interpretable as the transformed counterparts of the dark and light lumenal cells of the normal mammary epithelium. The phenotypical identity of the two categories has been assessed by in vitro cultivation (parallel paper). Many aberrant morphological variants, attributable to the two cell types, were observed at the tumour-stroma interface. We have therefore suggested that the high level of morphological heterogeneity may, at least in part, be the result of stromal influences on the gene expression of the transformed cells.

An ultrastructural evaluation of cell heterogeneity in invasive ductal carcinomas of the human breast. II. An in vitro study.

The ultrastructural characterization of the present continuous cell line, derived from a primary ductal infiltrating carcinoma (d.i.c.) of the human breast, has brought to light a remarkable morphological similarity with the original neoplastic cell population. A major parallelism is the permanent presence in culture of two categories of cells, exhibiting a strong isomorphism with the in vivo counterparts. The presence of well defined ultrastructural features, as duct-like structures, microvillous projections, junctional complexes and intracytoplasmic crypts, is a further confirmation of the breast cancer origin of this line. The significance and perspective of these findings are discussed.