Suppression of the Progression Phenotype by 5‐Azacytidine in Rat Embryo Cells Doubly Transformed by Type 5 Adenovirus and the Ha‐ras Oncogene^a

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

“…To evaluate the relationship between PEG-3 expression and transformation progression we have used a series of rodent cell lines that span the gamut from normal to highly progressed (Fisher et al, 1978;Babiss et al, 1985;Duigou et al, 1989;Reddy et al, 1993;Su et al, 1997Su et al, , 1999. A hallmark of the progression phenotype in this rodent model is the ability to grow with enhanced e ciency in an anchorage-independent manner and to induce tumors in nude mice with a reduced tumor latency time (18 ± 21 days as opposed to 38 ± 44 days, respectively) (Babiss et al, 1985;Su et al, 1999).…”

“…A useful model for de®ning the genetic and biochemical changes mediating tumor progression is the Ad5/early passage RE cell culture system (Fisher, 1984;Babiss et al, 1985;Duigou et al, 1989Duigou et al, , 1990Duigou et al, , 1991Fisher et al, 1979a,b,c;Reddy et al, 1993;Su et al, 1994Su et al, , 1997Kang et al, 1998a). Transformation of secondary rat embryo (RE) cells by Ad5 is often a sequential process resulting in the acquisition of and further elaboration of speci®c phenotypes by the transformed cell (Fisher et al, 1979a,b,c;Babiss et al, 1985).…”

“…Progression in the Ad5-transformation model is characterized by the development of enhanced anchorage-independence and tumorigenic capacity (as indicated by a reduced latency time for tumor formation in nude mice) (Fisher, 1984;Babiss et al, 1985). The progression phenotype in Ad5-transformed RE cells can be induced by selection for growth in agar or tumor formation in nude mice (Fisher et al, 1979a,b,c;Babiss et al, 1985), by transfection with oncogenes, such as Ha-ras, v-src, v-raf or the E6/E7 region of human papilloma virus type 18 (Duigou et al, 1989;Reddy et al, 1993) or by transfection with speci®c signal transducing genes, such as protein kinase C (Su et al, 1994). Progression, induced spontaneously or after gene transfer, is a stable cellular trait that remains undiminished in Ad5-transformed RE cells even after extensive passage (4100) in monolayer culture (Fisher, 1984;Babiss et al, 1985;Reddy et al, 1993).…”

“…Progression, induced spontaneously or after gene transfer, is a stable cellular trait that remains undiminished in Ad5-transformed RE cells even after extensive passage (4100) in monolayer culture (Fisher, 1984;Babiss et al, 1985;Reddy et al, 1993). However, a single-treatment with the demethylating agent 5-azacytidine (AZA) results in a stable reversion in transformation progression in 495% of cellular clones (Fisher, 1984;Babiss et al, 1985;Duigou et al, 1989;Reddy et al, 1993;Su et al, 1994). The progression phenotype is also suppressed in somatic cell hybrids formed between normal or un-progressed transformed cells and progressed cells (Duigou et al, 1990(Duigou et al, , 1991Reddy et al, 1993).…”

“…However, a single-treatment with the demethylating agent 5-azacytidine (AZA) results in a stable reversion in transformation progression in 495% of cellular clones (Fisher, 1984;Babiss et al, 1985;Duigou et al, 1989;Reddy et al, 1993;Su et al, 1994). The progression phenotype is also suppressed in somatic cell hybrids formed between normal or un-progressed transformed cells and progressed cells (Duigou et al, 1990(Duigou et al, , 1991Reddy et al, 1993). These ®ndings suggest that progression may result from the activation of speci®c progression-promoting (progression elevated) genes or the selective inhibition of progression-suppressing (progression suppressed) genes, or possibly a combination of both processes (Fisher, 1984;Babiss et al, 1985;Su et al, 1997;Kang et al, 1998a).…”