Polyadenylated RNAs of certain human tumour cell lines are shown to contain transcripts related to the cell-derived transforming onc genes of molecularly cloned primate, murine or avian transforming retrovirus genomes. Thus, analogues of retroviral transforming genes are both present and frequently expressed in human neoplastic cells.

Interleukin 3-dependent murine 32D cells do not detectably express members of the ErbB receptor family and do not proliferate in response to known ligands for these receptors. 32D transfectants were generated expressing human ErbB4 alone (32D.E4) or with ErbB2 (32D.E2͞E4). Epidermal growth factor (EGF), neuregulin 1-␤ (NRG1-␤), betacellulin (BTC), transforming growth factor-␣ (TGF-␣), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their ability to mediate mitogenesis in these transfectants. 32D.E4 responded mitogenically to NRG1-␤ and BTC. Surprisingly, EGF also induced significant DNA synthesis and TGF-␣ was negligibly mitogenic on 32D.E4 cells, whereas HB-EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in 32D.E2͞E4 cells did not significantly alter DNA synthesis in response to NRG1-␤ or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-␣ and unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that exhibited potent mitogenic activity on 32D.E2͞E4 cells at low concentrations induced adherence, morphological alterations, and up-regulation of the Mac-1 integrin and Fc␥RII͞III at higher concentrations. While 125 I-EGF could be specifically crosslinked to both 32D.E4 and 32D.E2͞E4 cells, its crosslinking capacity was greatly enhanced in the cotransfected cells. The ability of the various ligands to mediate proliferation and͞or adhesion in the two transfectants correlated with their capacity to induce substrate tyrosine phosphorylation and to initiate and sustain activation of mitogenactivated protein kinase. We conclude that the ability of ErbB4 to mediate signal transduction through EGF-like ligands is broader than previously assumed and can be profoundly altered by the concomitant expression of ErbB2.

The Jak1, Jak2, Jak3, and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin (IL)-4 stimulation in different cell systems. However, it is not clear which, if any, of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo. In the present study, we have utilized a mutant Jak1-deficient HeLa cell line, E1C3, and its pa-

Human tumors of a variety of histopathologic types have been established in tissue culture. The surface features of these cell lines were investigated by scanning electron microscopy (SEM) with the use of new techniques for specimen preparation. Tumor cells demonstrated striking degrees of surface activity with numerous microvilli, filopodia, blebs, and ruffles. Intercellular contacts were also prominent in cultures of most solid tumors observed by SEM. At low cell density, normal human fibroblasts exhibited some surface features such as microvilli and blebs, but at higher cell density they lacked extensive surface modifications. By transmission electron microscopy (TEM), the cytoskeleton of normal fibroblasts was shown to be well organized, with parallel orientation of microfilaments, filaments, and microtubules. These structures were also in tumor cells, but they lacked the degree of organization of fibroblasts. Desmosomes were readily demonstrated in normal fibroblasts and carcinoma cells in culture but not in sarcomas, melanomas, or tumors of neural origin. These studies have provided the first correlative SEM and TEM analyses of solid human tumor cells of diverse pathologic types in vitro.