Expression of c-erbB receptors, heregulin and oestrogen receptor in human breast cell lines.

Members of the c-erbB family have been implicated in poor prognosis in breast cancer. Given the propensity for heterodimerisation within the erbB family, the pattern of co-expression of these receptors is likely to be as functionally important as aberrant expression of any given receptor alone. Therefore, the patterns of expression of the receptors, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3, c-erbB-4, and one of the erbB ligands, heregulin (HRG), were examined in normal and malignant breast cell lines and compared with expression of oestrogen receptor (ER), a classical indicator of good prognosis. There was an inverse correlation between ER and EGF-R mRNA levels, as previously described, but no correlation between either of these receptors and c-erbB-2. c-erbB-3 expression was positively correlated with ER. In contrast, HRG expression was inversely related to ER. Expression of antisense-ER resulted in increased EGF-R mRNA, demonstrating a functional link between the expression of these 2 genes, however, there was no significant change in c-erbB-2 or c-erbB-3 mRNA, suggesting that ER is not directly involved in control of expression of these genes. A comparison of individual erbB receptors and HRG revealed that the majority of lines expressing increased levels of c-erbB-2 also expressed elevated levels of c-erbB-3 mRNA, and none of the cell lines that expressed both c-erbB-2 and either c-erbB-3 or c-erbB-4 expressed the ligand HRG. In summary, the levels of expression of c-erbB-1, -2, -3, and -4 varied in this series of breast cell lines, and the pattern of expression and the relationship of each growth factor receptor to the expression of ER was quite distinct. The lack of expression of HRG in cell lines that express receptors may be indicative of paracrine interactions between erbB ligands and their cognate receptors and may suggest that the ligand and receptors are expressed in different subtypes of breast epithelial cells from which the cell lines are derived.

[Anomalous implantation of the appendiceal base. A case report]. / Anomalia di impianto della base appendicolare. Descrizione di un caso.

The authors report a case of anomalous appendicular implantation observed in a 17-year-old male. The appendix was not found in its usual site, but upon the antero-lateral wall of ascending colon, 15 cm from the junction of the taenia of caecum. A partial mobilization of caecum was required for appendectomy. By a review of recent bibliography this anomaly seems very unusual considering the poor number of reports in literature. The anatomy and embryology of the vermiform appendix are briefly presented, and at the same time the possible pathogenetic hypothesis of this anomaly, such as described by other colleagues. The authors underscore how, knowledge of another case report, in their experience, suggested to search for appendix in an unusual site, before concluding for an appendicular agenesis.

Expression and amplification of cyclin genes in human breast cancer.

Cyclins, the regulatory subunits of cyclin-dependent kinases, play an important role in the control of cellular proliferation. Since dysregulated expression of these genes may contribute to the malignant phenotype the expression and amplification of cyclin A, B1, C, D1, D2, D3 and E genes were studied in 20 breast cancer cell lines. Increased expression of one or more of the cyclin A, B1, D1 or E genes was found in seven cell lines (35%); of these five (25%) showed increased expression of cyclin D1. Overexpression occurred in both the presence and absence of gene amplification. Conversely, amplification did not invariably lead to overexpression. Cyclin D2 expression was lower in breast cancer cell lines than in cultured normal breast epithelial cells. Cyclin D1 expression was further investigated in breast tumour biopsies: 56 of 124 specimens (45%) expressed higher levels of cyclin D1 mRNA than normal breast tissue. These data implicate dysregulated expression of several cyclin genes, particularly cyclin D1, as a potential factor in the pathogenesis of breast cancer.