Cancer cells (Cold Spring Harbor, N.Y. : 1989)最新文献

Cathepsin D is a ubiquitously expressed lysosomal protease. Initially synthesized as an inactive precursor of 52 kD (pro-cathepsin D), the enzyme is subsequently converted to its active forms by proteolytic processing. Breast cancer cells, unlike normal cells, secrete high levels of pro-cathepsin D; this abnormal secretion is due to both overexpression of the gene and altered processing of the protein. Recent transfection experiments indicate that overexpression of cathepsin D can increase the metastatic potential of tumor cells in nude mice. This study complements clinical studies, which have shown than high cathepsin D concentrations in the cytosol of primary breast cancers may be predictive of subsequent metastasis, particularly for patients with axillary node-negative tumors. These results, and the potential mechanisms by which cathepsin D may promote metastasis, are considered here.

Different activities of DNA viral gene products seem to be involved in the immortalization process, even in cases where continued presence of the viral genome does not seem to be required for the maintenance of the immortalized state of a cell. Immortalization, does not appear to represent a single event as implied earlier and several studies have shown that the process can be reversible. Polyomavirus large T antigen and HPV E7 (or E6 + E7) seem to possess all the activities required in vitro for immortalization of human cells, whereas one of the required activities--that defined in the two-step model as a rare mutagenic event which occurs during cellular crisis--is weaker in SV40 large T antigen and E1A. Viral functions that can activate PCNA expression (or repress Rb1 expression) have to be considered as pivotal activities in immortalization. Finally, the growth factor independence characterizing many immortalized cells could be a result of growth factor-like activities intrinsic to the viral proteins or could reflect their ability to induce autocrine growth mechanisms. These statements all relate to the first aspect of our initial hypothesis concerning cellular immortalization and in general substantiate it. Is immortalization an essential step in malignant transformation? There seems no a priori reason that transformation or tumorigenesis should depend upon cellular immortalization. Notably, many tumors appear to be mortal in culture. Growth factor independence or activation of DNA replication--essential features of immortalization--are probably of little importance for tumors in vivo where a crucial environment is supplied by the surrounding cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The data reviewed at this meeting reinforce the notion that HBV may contribute to the development of liver cancer through a variety of mechanisms, including activation of oncogenes (c-myc and N-myc) by insertional mutagenesis, expression of viral proteins (X and pre-S2/S) that function as trans-activators and possibly oncoproteins, and introduction of chromosomal defects through enzymatically mediated integration into the host genome. Not all of these mechanisms appear to be active in every tumor, however. Thus, future work will be aimed at characterizing each mechanism in more detail and determining its relative importance in the carcinogenic process.

Changes in cellular gene transcription patterns induced by extracellular signals are thought to be important for many biological processes, including the control of cell growth. The transmission of gene regulatory signals through the cytoplasm is mediated by signaling pathways, of which protein kinases are important components, and recent evidence suggests that communication between the cytoplasm and nucleus relies on signal-dependent phosphorylation and dephosphorylation of transcription factors. This new information is reviewed and the implications for gene regulation and the control of cell growth are discussed.

Prostatic cancer is an increasing medical problem. Investigations of the biology of the prostate and the development of prostate cancer have shown that the prostate gland contains high levels of polypeptide growth factors, especially members of the fibroblast growth factor (FGF) and transforming growth factor (TGF)-beta family. Activated oncogenes and elevated proto-oncogene activities including ras and myc have been detected in human prostate cancer tissues, but there is no consensus as to the predominant genetic alterations involved in the progression of this disease. In vivo animal models have shown that relevant growth factors and oncogenes can induce both premalignant and malignant changes in prostate tissue. Additional experimental and clinical studies are needed to present a clearer molecular profile of this important malignancy.