Activated oncogenes

Reynolds SH, Stowers SJ, Patterson RM, et al. 1987. Activated oncogenes in B6C3F, mouse liver tumors Implications for risk assessment. Science 237 1309-1316. 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

Hunt The other corollary is, have you tried putting other activated oncogenes of the signalling variety (such as ras and src) into these cells to make them independent of the exogenous signalling molecules ... 

Jeeeord, C. E., etal., Nudear-cytoplasmic translocation of BARDl is linked to its apoptotic activity. Oncogene, 2004, 23(20), 3509-20. 

Lucas L., Hemandez-Alcoceba, R., Penalva, V., and Lacal, J.C., 2001, Modulation of phosphohpase D by hexadecylphosphorylchohne a putative novel mechanism for its antitumoral activity. Oncogene 20 1110-1117... 

Sugiyama K, Sugiura K, Kara T, Sugimoto K, Shima H, Honda K, Furukawa K, Yamashita S, Urano T (2002) Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene... 

Dominant, gain-of-function mutations that activate oncogenes confer a rapid-growth phenotype on cells. 

Activated oncogenes are rarely passed through the germline. 

Multiple mutations that activate oncogenes or inactivate tumor suppressor genes accumulate due to progressive loss of DNA repair mechanisms and cell cycle control. 

More recent studies have found that the first treatment with DMBA causes a mutation in the H-ras proto-oncogene, causing it to become an active oncogene. 

Of course, if the adducts are formed in sections of DNA that are "junk" DNA or spacing sections, there may be no consequence, even if not repaired. However, if the unrepaired DNA adduct(s) is in a section of DNA that is part of a tumor suppressor gene or a pro to-oncogene, then more serious changes may result such as the initiation of a tumor. In fact, benzo [a] pyrene does cause mutations (G to T trans vers ions) in the 12 th codon of one of the ras protooncogenes. This could convert the proto-oncogene into an active oncogene. 

Hobbs SS, Coffing SL, Le AT, Cameron EM, Williams EE, et al. 2002. Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation. Oncogene 21 8442-8452. 

Berns K, Hijmans EM, Bernards R. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of 54. cyclin E/CDK2 kinase activity. Oncogene 1997 15 1347-1356. 

Kirsten-ras is the most frequently activated oncogene in human tumors (1). Activated K-ras is bound to GTP and possesses intrinsic GTPase activity which leads to its inactivation. Oncogenic K-ras has dramatically lower... 

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