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p21ras Herault et al. (1993, 1995) reported a significant association between autism and the larger fragments of the c-Harvey-Ras oncogene (p21ras), a member of the G-protein subfamily. The ras oncogene is thought to be responsible for 40% of all colon cancers, as well as 90% of pancreatic cancers. It has further been identified in breast, bladder and prostate cancers. It has been shown that p21ras mediates its transforming effects by constitutive activation of proliferative signal transduction pathways, such as adenylate cyclase. Studies done with pasteurella multocida toxin (rPMT)- one of the most potent mitogenic substances known for fibroblasts in vitro - showed the Gq/11 family heterotrimeric G proteins to induce Ras-dependent Erk activation via protein kinase C-independent "transactivation" of the epidermal growth factor receptor (Seo et al, 2000). GTP-binding is required for the transforming activity of ras p21 and by extension for the normal function of the proto-oncogene product (Lacal et al, 1986). Studer et al (1992) identified ALL thyroid goiter nodules to contain areas where the epithelial cells were morphologically grossly altered and heavily loaded with p21ras. Fluoride compounds are known and established p21ras pathway activators. Gq/11: Gq/11 and ras pathways are established to share mediation of certain pathways/conditions (i.e. LaMorte et al, 1994; Seo et al, 2000). ================================== ========== Herault J, Perrot A, Barthelemy C, Buchler M, Cherpi C, Leboyer M, Sauvage D, Lelord G, Mallet J, Muh JP - "Possible association of c-Harvey-Ras-1 (HRAS-1) marker with autism" Psychiatry Res 46(3):261-7 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8098541&form=6&db=m&Dopt=r Herault J, Petit E, Martineau J, Perrot A, Lenoir P, Cherpi C, Barthelemy C, Sauvage D, Mallet J, Muh JP - "Autism and genetics: clinical approach and association study with two markers of HRAS gene" Am J Med Genet 60(4):276-81 (1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7485261&form=6&db=m&Dopt=r Lacal JC, Anderson PS, Aaronson SA - "Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities" EMBO J 5(4):679-87 (1986) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3011420&form=6&db=m&Dopt=r LaMorte VJ, Thorburn J, Absher D, Spiegel A, Brown JH, Chien KR, Feramisco JR, Knowlton KU - "Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1-adrenergic stimulation" Biol Chem 269(18):13490-6(1994) Studer H, Gerber H, Zbaeren J, Peter HJ - "Histomorphological and
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