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June 1, 1994, Vol 271, No. 21 >
ARTICLE | June 1, 1994

Oncology and Hematology FREE

Judith E. Karp, MD; Samuel Broder, MD
JAMA. 1994;271(21):1693-1695. doi:10.1001/jama.1994.03510450065036
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References

Cell division, differentiation, survival, and programmed death are determined by growth factor-triggered cascades of convergent signaling pathways. The function of a cell depends on molecular messages moving from the extracellular space across the cell membrane through the cytoplasm and into the nucleus, where those messages modulate net gene expression. At least two pivotal intracellular components are activated during the early steps of the signaling cascade: (1) protein tyrosine kinases (PTKs), some of which form the internal domains of many membrane-spanning growth factor receptors, others of which act within the cytoplasm, and all of which are commonly encoded by growth-promoting oncogenes, and (2) membrane-associated G proteins encoded by the ras family of oncogenes. Net overexpression or derangements of PTK-encoding oncogenes (eg, c-src, c-abl, c-kit, and the erb family) and ras serve as critical driving forces in the evolution of many epithelial and lymphohematopoietic cancers.

Many investigators have now demonstrated a crucial

REFERENCES

1 +
Buday L, Downward J.  Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell . 1993;;73:611-620.
2 +
Chardin P, Camonis JH, Gale N, et al.  Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science . 1993;;260:1338-1343.
3 +
Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA.  Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature . 1993;;363:45-51.
4 +
Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Bar-Sagi D.  Grb2 mediates EGF-c dependent activation of guanine nucleotide exchange on Ras. Nature . 1993;; 363:88-92.
5 +
Li N, Batzer A, Daly R, et al.  Guanine nucleotide-releasing factor hSosl binds to Grb2 and links tyrosine kinases to Ras signalling. Nature . 1993;;363:85-88.
6 +
Olivier JP, Raabe T, Henkemeyer M, et al.  A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell . 1993;:73:179-191.
7 +
Rozakis-Adcock M, Fernley R, Wade J, Pawson T, Bowtell D.  The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSosl. Nature . 1993;;363:83-85.
8 +
Simon MA, Dodson GS, Rubin GM.  An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Cell . 1993;;73:169-177.
9 +
Daley GQ, Van Etten RA, Baltimore D.  Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science . 1990;; 247:824-830.
10 +
Gishizky ML, Witte ON.  Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitro. Science . 1992;;256:836-839.
11 +
Pendergast AM, Quilliam LA, Cripe LD, et al.  BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell . 1993;;75:175-185.
12 +
Diekmann D, Brill S, Garrett MD, et al.  Bcr encodes a GTPase-activating protein for p21ras. Nature . 1991;;351:400-402.
13 +
Lu BD, Liu J, Campbell M, et al.  Tyrosine phosphorylation of P160 BCR by P210 BCR-i ABL. Blood . 1993;;82:1257-1263.
14 +
Cicchetti P, Mayer BJ, Thiel G, Baltimore D.  Identification of a protein that binds to the SH2 region of Abl and is similar to Ber and GAP-rho. Science . 1992;;257:803-806.
15 +
Druker B, Okuda K, Matulonis U, Salgia R, Roberts T, Griffin JD.  Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines. Blood . 1992;;79:2215-2220.
16 +
Mandanas RA, Leibowitz DS, Gharehbaghi K, et al.  Role in p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood . 1993;;82:1838-1847.
17 +
Khosvari-Far R, Cox AD, Kato K, Der CJ.  Protein prenylation: key to ras function and cancer intervention? Cell Growth Differ . 1992;;3:461-469.
18 +
Haag JD, Lindstrom MJ, Gould MN.  Limonene-induced regression of mammary carcinomas. Cancer Res . 1992;;52:4021-4026.
19 +
James GL, Goldstein JL, Brown MS, et al.  Benzodiazepine peptidomimetics: potent inhibitors of ras farnesylation in animal cells. Science . 1993;;260:1937-1942.
20 +
Kohl NE, Mosser SD, deSolms SJ, et al.  Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science . 1993;;260:1934-1937.
21 +
Samid D, Shack S, Myers CE.  Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest . 1993;;91:2288-2295.
22 +
Paquette RL, Landaw EM, Pierre RV, et al.  N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndromes. Blood . 1993;;82:590-599.
23 +
Lupu R, Colomer R, Zugmaier G, et al.  Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. Science . 1990;;249:1552-1555.
24 +
Wen D, Peles E, Cupples R, et al.  Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell . 1992;;69:559-572.
25 +
Holmes WE, Sliwkowski MX, Akita RW, et al.  Identification of heregulin, a specific activator of p185erbB2. Science . 1992;;256:1205-1210.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Buday L, Downward J.  Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell . 1993;;73:611-620.
2 +
Chardin P, Camonis JH, Gale N, et al.  Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science . 1993;;260:1338-1343.
3 +
Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA.  Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature . 1993;;363:45-51.
4 +
Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Bar-Sagi D.  Grb2 mediates EGF-c dependent activation of guanine nucleotide exchange on Ras. Nature . 1993;; 363:88-92.
5 +
Li N, Batzer A, Daly R, et al.  Guanine nucleotide-releasing factor hSosl binds to Grb2 and links tyrosine kinases to Ras signalling. Nature . 1993;;363:85-88.
6 +
Olivier JP, Raabe T, Henkemeyer M, et al.  A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell . 1993;:73:179-191.
7 +
Rozakis-Adcock M, Fernley R, Wade J, Pawson T, Bowtell D.  The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSosl. Nature . 1993;;363:83-85.
8 +
Simon MA, Dodson GS, Rubin GM.  An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Cell . 1993;;73:169-177.
9 +
Daley GQ, Van Etten RA, Baltimore D.  Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science . 1990;; 247:824-830.
10 +
Gishizky ML, Witte ON.  Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitro. Science . 1992;;256:836-839.
11 +
Pendergast AM, Quilliam LA, Cripe LD, et al.  BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell . 1993;;75:175-185.
12 +
Diekmann D, Brill S, Garrett MD, et al.  Bcr encodes a GTPase-activating protein for p21ras. Nature . 1991;;351:400-402.
13 +
Lu BD, Liu J, Campbell M, et al.  Tyrosine phosphorylation of P160 BCR by P210 BCR-i ABL. Blood . 1993;;82:1257-1263.
14 +
Cicchetti P, Mayer BJ, Thiel G, Baltimore D.  Identification of a protein that binds to the SH2 region of Abl and is similar to Ber and GAP-rho. Science . 1992;;257:803-806.
15 +
Druker B, Okuda K, Matulonis U, Salgia R, Roberts T, Griffin JD.  Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines. Blood . 1992;;79:2215-2220.
16 +
Mandanas RA, Leibowitz DS, Gharehbaghi K, et al.  Role in p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood . 1993;;82:1838-1847.
17 +
Khosvari-Far R, Cox AD, Kato K, Der CJ.  Protein prenylation: key to ras function and cancer intervention? Cell Growth Differ . 1992;;3:461-469.
18 +
Haag JD, Lindstrom MJ, Gould MN.  Limonene-induced regression of mammary carcinomas. Cancer Res . 1992;;52:4021-4026.
19 +
James GL, Goldstein JL, Brown MS, et al.  Benzodiazepine peptidomimetics: potent inhibitors of ras farnesylation in animal cells. Science . 1993;;260:1937-1942.
20 +
Kohl NE, Mosser SD, deSolms SJ, et al.  Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science . 1993;;260:1934-1937.
21 +
Samid D, Shack S, Myers CE.  Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest . 1993;;91:2288-2295.
22 +
Paquette RL, Landaw EM, Pierre RV, et al.  N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndromes. Blood . 1993;;82:590-599.
23 +
Lupu R, Colomer R, Zugmaier G, et al.  Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. Science . 1990;;249:1552-1555.
24 +
Wen D, Peles E, Cupples R, et al.  Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell . 1992;;69:559-572.
25 +
Holmes WE, Sliwkowski MX, Akita RW, et al.  Identification of heregulin, a specific activator of p185erbB2. Science . 1992;;256:1205-1210.

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