Oncogenic transformation

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

All morphologically transformed cell lines tested were able to proliferate in soft agar and formed tumors in nude mice. 

Similar cloning of normal cultures was unsuccessful, and none of the normal mass cultures derived from hamster embryos, and tested for colony formation in soft agar or formation of tumors in nude mice were positive. 

Test Compounds. Nickel subsulfide (crystalline oNi3S2, particle size 5 ym) was provided by Dr. Edward Kostiner, University of Connecticut, and its purity and crystal structure were verified by emission spectroscopy and X-ray diffractometry as previously described (L5 - Amorphous nickel monosulfide (NiS) was precipitated by addition of aimnonium sulfide to a solution of NiCl2 that was prepared from carbonyl-derived Ni dust and ultrapure HCl. The amorphous NiS was devoid of crystal structure, based upon X-ray diffractometry. The aNi3 2 and NiS powders were sterilized by washing in acetone immediately prior to suspension in tissue culture medium. 

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Some established cell lines were derived from malignant tissue. Many of these cell lines can form tumors when injected into susceptible animals. Other established cell lines are not Uunorigenic. However, exposure to carcinogens, and irradiation can cause these cells to form tumors in susceptible animals. In addition, transformation can be caused by spontaneous mutations, by growth factors, and by viral (or oncogenic) transformation (Table 6). Malignant transformation is defined as consisting of the series of events that cause normal cells to develop the capacity to form tumors. 

Newrzela S, Cornils K, Li Z, Baum C, Brugman MH, Hartmann M, Hartmann S, Hansmann ML, Fehse B, von Laer D (2008) Resistance of mature T cells to oncogene transformation. Blood 112 2278-2286... 

Law, B.K. et al. (2002) Rapamycin potentiates transforming growth factor P-induced growth arrest in nontransformed, oncogene-transformed, and human cancer cells. Mol. Cell. Biol. 22, 8184-8198. 

Benhar, M. et al., Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress, Mol. Cell. Biol., 21, 6913, 2001. 

However, as with many stories in science, caveolin expression and oncogenic transformation are a complex and controversial tale. Indeed, numerous other types of cancer cells display increased caveolin-1 expression. For example, caveolin-1 expression has been reported to be overexpressed in several cancers including prostate and breast [52], lung [53], and bladder [54], to name a few. What to make of the dizzying array of caveolin expression data in the context of cancer from a diagnostic or therapeutic standpoint at this time is unclear. 

A. J. Koleske, D. Baltimore, and M. P. Lisanti. Reduction of caveolin and caveolae in oncogenically transformed cells. Proc. Natl. Acad. Sci. USA 92 1381-1385 (1995). 

Park J, Wood M A, Cole MD (2002) BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Mol Cell Biol 22 1307-1316 Park JH, Roeder RG (2006) GAS41 Is Required for Repression of the p53 Tumor Suppressor Pathway... 

Rai, S., Duh, F., Vigdorovich, V., Danilkovitch-Miagkova, A., Lerman, M. and Miller, A. (2001) Candidate tumor suppressor HYAL2 is a glycosylphospha-tidylinositol (GPI)- anchored cell-surface receptor for Jaagsietke sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc. Natl. Acad. Sci, f/Y4 98, 4443-4448. 

Oncogene-transformed mouse fibroblasts have a more decondensed chromatin structure than parental cell lines [59]. Phosphorylated Hl -3 levels are elevated in oncogene (ras, raf, fes, mos, myc) and aberrantly expressed MAPKK (MEK) transformed mouse fibroblasts, which have elevated activities of MAPK (ERKl and 2) [59] (Fig. 6). Further, RZ)-deficient human fibroblasts have increased levels of phosphorylated HI and a relaxed chromatin structure [60]. Cyclin E-Cdk2 was directly involved in increasing the levels of phosphorylated HI [60]. Elevated cyclin E-Cdk2 activity resulting from persistent activation of the Ras-MAPK pathway is also responsible for increased level of phosphorylated HI in oncogene-transformed mouse fibroblasts [61]. 

Whitesell, L., E. G. Mimnaugh, B. De Costa, C. E. Myers, and L. M. Neckers. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA. 91 8324-8.1994. 

Basu A, Cline JS (1995) Oncogenic transformation alters cisplatin induced apoptosis in rat embryo fibroblasts. Int J Cancer 63 597-603 Basu A, Weixel KM (1995) Comparison of protein kinase C activity and isoform expression in cisplatin-sensitive and -resistant ovarian carcinoma cells. Int J Cancer 62 457-460... 

Saxholm HJK, Reith A, Brogger A. 1981. Oncogenic transformation and cell lysis in C3H/10T1/2 cells and increased sister chromatid exchange in human lymphocytes by nickel subsullide. Cancer Res 41 4136-4139. 

NT089 Piao, C. Q., and T. K. Hei. The biological effectiveness of radon daughter alpha particles. 1. Radon, cigarette smoke and oncogenic transformation. Carcinogenesis 1993 14(3) 497—501. 

In comparison to the level of cellular serine or threonine phosphorylation, protein tyrosine phosphorylation occurs at quite low levels in normal cells but dramatically increases upon oncogenic transformation or stimulation. Since the first discovery in 1978 that the transforming protein from Rous sarcoma virus (pp60vsrc) exhibited intrinsic kinase activity/5 protein kinase activity has also been shown to be inherent to other growth factor receptors such as epidermal growth factor receptor and the insulin receptor,[6 91 and to involve autophosphorylation processes. The diverse biochemical activity exhibited by protein tyrosine phosphorylation has stimulated the development of chemical methods for the preparation of phosphorylated peptides for use as substrates in elucidating the biochemical and physiological activity of phosphorylated site(s). 

Bertram, J.S. and Heidelberger, C. (1974). Cell cyclic dependency of oncogenic transformation induced by N-methyl-N -nitio-N-nitrosoguanidine in culture, Cancer Res. 34,526. 

Miller, R.C., Hall, E.J., and Rossi, H.H. (1979). "Oncogenic transformation in mammalian cells in vitro with split doses of x rays, Proc. NatL Acad. Sd., 76,5755. 

Steele, V.E., IVIarchok, A.C., and Nettensheim, P. (1979). Oncogenic transformation in epithelial cell lines derived from tracheal explants exposed in vitro to N-methyl-N-nitro N nitrosoguanine, Cancer Res. 39,3805. 

Terzaghi, M. and Little, J.B. (1976a). Oncogenic transformation after split dose x-irradiation, Int. J. Radiat. BioL 29, 583. 

Models with genetically induced sensitivity to oncogenic transformation serve as sensitive indicators of carcinogenic agents. 

In female mammalian cells most of the genes on one of the two X-chromosomes are completely inactivated. DNA methylation plays a major role in this process.244 245 A perfect correlation has been observed between 5 -methylation of cytosines in CpG islands and inactivation of X-chromosome genes.246 Methylation may also play a role in recombination and repair.247 Methylation of DNA decreases with increasing age.248 It increases as a result of oncogenic transformation of cells.249 Some other modifications of DNA largely limited to bacteriophages are discussed on p. 234 247/250... 

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