Basal cell carcinomas in mice overexpressing sonic hedgehog

Science

Volumn 276, Issue 5313, 1997, Pages 817-821

  Oro, Anthony E ^a   Higgins, Kay M ^a   Hu, Zhilan ^b   Bonifas, Jeannette M ^b   Epstein Jr , Ervin H ^b   Scott, Matthew P ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SONIC HEDGEHOG PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BASAL CELL CARCINOMA; BASAL CELL NEVUS SYNDROME; CONTROLLED STUDY; DROSOPHILA; GENE MUTATION; METASTASIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; SKIN CARCINOGENESIS; TRANSGENIC MOUSE; TUMOR SUPPRESSOR GENE;

ANIMALS; BASAL CELL NEVUS SYNDROME; CARCINOMA, BASAL CELL; EMBRYO; GENE EXPRESSION REGULATION, NEOPLASTIC; HEDGEHOG PROTEINS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; KERATINOCYTES; MALE; MEMBRANE PROTEINS; MICE; MICE, SCID; MICE, TRANSGENIC; MUTATION; NEOPLASM TRANSPLANTATION; PROTEIN BIOSYNTHESIS; PROTEINS; RECEPTORS, CELL SURFACE; SKIN; SKIN NEOPLASMS; SKIN TRANSPLANTATION; TRANS-ACTIVATORS;

ANIMALIA; DROSOPHILA MELANOGASTER; ERINACEIDAE; MUS MUSCULUS;

EID: 0030955557     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.276.5313.817     Document Type: Article

References (60)

1. E. Fearon and B. Vogelstein, Cell 61, 759 (1990); K. Kinzler and B. Vogelstein, ibid. 87, 159 (1996).
2. E. Fearon and B. Vogelstein, Cell 61, 759 (1990); K. Kinzler and B. Vogelstein, ibid. 87, 159 (1996).
3. B. Barlogie et al., Cancer Res. 43, 3982 (1983); R. Marks, G. Rennie, T. Selwood, Arch. Dermatol. 124, 1039 (1988); S. J. Miller, J. Am. Acad. Dermatol. 24, 161 (1991); D. Miller and M. Weinstock, ibid. 30, 774 (1994).
4. B. Barlogie et al., Cancer Res. 43, 3982 (1983); R. Marks, G. Rennie, T. Selwood, Arch. Dermatol. 124, 1039 (1988); S. J. Miller, J. Am. Acad. Dermatol. 24, 161 (1991); D. Miller and M. Weinstock, ibid. 30, 774 (1994).
5. B. Barlogie et al., Cancer Res. 43, 3982 (1983); R. Marks, G. Rennie, T. Selwood, Arch. Dermatol. 124, 1039 (1988); S. J. Miller, J. Am. Acad. Dermatol. 24, 161 (1991); D. Miller and M. Weinstock, ibid. 30, 774 (1994).
6. B. Barlogie et al., Cancer Res. 43, 3982 (1983); R. Marks, G. Rennie, T. Selwood, Arch. Dermatol. 124, 1039 (1988); S. J. Miller, J. Am. Acad. Dermatol. 24, 161 (1991); D. Miller and M. Weinstock, ibid. 30, 774 (1994).
7. R. Gorlin, Dermatol. Clin. 13, 113 (1995).
8. H. Hahn et al., Cell 85, 841 (1996); R. L. Johnson et al., Science 272, 1668 (1996); A. Unden et al., Cancer Res. 56, 4562 (1996); A. Chidambaram et al., ibid., p. 4599.
9. H. Hahn et al., Cell 85, 841 (1996); R. L. Johnson et al., Science 272, 1668 (1996); A. Unden et al., Cancer Res. 56, 4562 (1996); A. Chidambaram et al., ibid., p. 4599.
10. H. Hahn et al., Cell 85, 841 (1996); R. L. Johnson et al., Science 272, 1668 (1996); A. Unden et al., Cancer Res. 56, 4562 (1996); A. Chidambaram et al., ibid., p. 4599.
11. H. Hahn et al., Cell 85, 841 (1996); R. L. Johnson et al., Science 272, 1668 (1996); A. Unden et al., Cancer Res. 56, 4562 (1996); A. Chidambaram et al., ibid., p. 4599.
12. A. G. Quinn, C. Campbell, E. Healy, J. L. Rees, J. Invest. Dermatol. 102, 300 (1994); M. Gailani et al., Nature Genet. 14, 78 (1996).
13. A. G. Quinn, C. Campbell, E. Healy, J. L. Rees, J. Invest. Dermatol. 102, 300 (1994); M. Gailani et al., Nature Genet. 14, 78 (1996).
14. P. W. Ingham, Curr. Opin. Genet. Dev. 5, 492 (1995); M. Dean, Nature Genet. 14, 245 (1996); N. Perrimon, Cell 86, 513 (1996); M. Hammerschmidt, A. Brook, A. P. McMahon, Trends Genet. 13, 14 (1997).
15. P. W. Ingham, Curr. Opin. Genet. Dev. 5, 492 (1995); M. Dean, Nature Genet. 14, 245 (1996); N. Perrimon, Cell 86, 513 (1996); M. Hammerschmidt, A. Brook, A. P. McMahon, Trends Genet. 13, 14 (1997).
16. P. W. Ingham, Curr. Opin. Genet. Dev. 5, 492 (1995); M. Dean, Nature Genet. 14, 245 (1996); N. Perrimon, Cell 86, 513 (1996); M. Hammerschmidt, A. Brook, A. P. McMahon, Trends Genet. 13, 14 (1997).
17. P. W. Ingham, Curr. Opin. Genet. Dev. 5, 492 (1995); M. Dean, Nature Genet. 14, 245 (1996); N. Perrimon, Cell 86, 513 (1996); M. Hammerschmidt, A. Brook, A. P. McMahon, Trends Genet. 13, 14 (1997).
18. T. Hall, J. Porter, P. Beachy, D. Leahy, Nature 378, 212 (1996).
19. P. Ingham, ibid. 366, 560 (1993).
20. M. J. Bitgood and A. P. McMahon, Dev. Biol. 172, 126 (1995); S. Iseki et al., Biochem. Biophys. Res. Commun. 218, 688 (1996).
21. M. J. Bitgood and A. P. McMahon, Dev. Biol. 172, 126 (1995); S. Iseki et al., Biochem. Biophys. Res. Commun. 218, 688 (1996).
22. The accumulation of Shh RNA is seen ectodermally later in development and in the anagen hair matrix, with ptc RNA accumulating in adjacent cells.
23. The Eco RI-Spe 1 fragment of the mouse Shh cDNA, which includes the entire cDNA and the first 400 base pairs (bp) of the 3′ untranslated region, was placed into the keratin β-globin promoter cassette (12). The cassette was microinjected into the pronucleus of B6CBF2 zygotes, and transgenic embryos were identified by standard techniques.
24. C. Byrne and E. Fuchs, Development 120, 2369 (1994); M. Saitou et al., Nature 374, 159 (1995).
25. C. Byrne and E. Fuchs, Development 120, 2369 (1994); M. Saitou et al., Nature 374, 159 (1995).
26. J. C. Izpisua-Belmonte, D. A. Ede, C. Tickle, D. Duboule, Development 114, 959 (1992);
27. P. H. Francis-West et al., Dev. Dyn. 203, 187 (1995).
28. Rib abnormalities, such as abnormal fusion at the sternum, and lower jaw aplasia were also commonly seen.
29. W. F. Lever and G. S. Lever, Histopathology of the Skin (Lippincott, Philadelphia, 1990); S. Miller, J. Am. Acad. Dermatol. 24, 1 (1991).
30. W. F. Lever and G. S. Lever, Histopathology of the Skin (Lippincott, Philadelphia, 1990); S. Miller, J. Am. Acad. Dermatol. 24, 1 (1991).
31. A. C. Markey, E. B. Lane, D. M. MacDonald, I. M. Leigh, Br. J. Dermatol. 126, 154 (1992).
32. A. Stoler, R. Kopan, M. Duvic, E. Fuchs, J. Cell. Biol. 107, 427 (1988).
33. J. Stanley, J. Beckwith, R. Fuller, S. Katz, Cancer 50, 1486 (1982); P. Savoia, L. Trusolino, E. Pepino, O. Cremona, P. Marchisio, J. Invest. Dermatol. 101, 352 (1993); Z. Lazarova, N. Domloge-Hultsch, K. Yancey, Exp. Dermatol. 4, 121 (1995); J. Fairley, P. Heintz, M. Neuburg, L. Diaz, G. Giudice, Br. J. Dermatol. 133, 385 (1995).
34. J. Stanley, J. Beckwith, R. Fuller, S. Katz, Cancer 50, 1486 (1982); P. Savoia, L. Trusolino, E. Pepino, O. Cremona, P. Marchisio, J. Invest. Dermatol. 101, 352 (1993); Z. Lazarova, N. Domloge-Hultsch, K. Yancey, Exp. Dermatol. 4, 121 (1995); J. Fairley, P. Heintz, M. Neuburg, L. Diaz, G. Giudice, Br. J. Dermatol. 133, 385 (1995).
35. J. Stanley, J. Beckwith, R. Fuller, S. Katz, Cancer 50, 1486 (1982); P. Savoia, L. Trusolino, E. Pepino, O. Cremona, P. Marchisio, J. Invest. Dermatol. 101, 352 (1993); Z. Lazarova, N. Domloge-Hultsch, K. Yancey, Exp. Dermatol. 4, 121 (1995); J. Fairley, P. Heintz, M. Neuburg, L. Diaz, G. Giudice, Br. J. Dermatol. 133, 385 (1995).
36. J. Stanley, J. Beckwith, R. Fuller, S. Katz, Cancer 50, 1486 (1982); P. Savoia, L. Trusolino, E. Pepino, O. Cremona, P. Marchisio, J. Invest. Dermatol. 101, 352 (1993); Z. Lazarova, N. Domloge-Hultsch, K. Yancey, Exp. Dermatol. 4, 121 (1995); J. Fairley, P. Heintz, M. Neuburg, L. Diaz, G. Giudice, Br. J. Dermatol. 133, 385 (1995).
37. M. Cooper and H. Pinkus, Cancer Res. 37, 2544 (1977); R. E. Grimwood et al., Cancer 56, 519 (1985); G. Stamp, A. Quaba, A. Braithwaite, N. A. Wright, J. Pathol. 156, 213 (1988); S. Hales, G. Stamp, M. Evans, K. Fleming, Br. J. Dermatol. 120, 351 (1989).
38. M. Cooper and H. Pinkus, Cancer Res. 37, 2544 (1977); R. E. Grimwood et al., Cancer 56, 519 (1985); G. Stamp, A. Quaba, A. Braithwaite, N. A. Wright, J. Pathol. 156, 213 (1988); S. Hales, G. Stamp, M. Evans, K. Fleming, Br. J. Dermatol. 120, 351 (1989).
39. M. Cooper and H. Pinkus, Cancer Res. 37, 2544 (1977); R. E. Grimwood et al., Cancer 56, 519 (1985); G. Stamp, A. Quaba, A. Braithwaite, N. A. Wright, J. Pathol. 156, 213 (1988); S. Hales, G. Stamp, M. Evans, K. Fleming, Br. J. Dermatol. 120, 351 (1989).
40. M. Cooper and H. Pinkus, Cancer Res. 37, 2544 (1977); R. E. Grimwood et al., Cancer 56, 519 (1985); G. Stamp, A. Quaba, A. Braithwaite, N. A. Wright, J. Pathol. 156, 213 (1988); S. Hales, G. Stamp, M. Evans, K. Fleming, Br. J. Dermatol. 120, 351 (1989).
41. We performed mouse skin grafts as in (27), except that we used transgenic or wild-type dorsal trunk skin from B6CBF2 embryos that had been dissected away from underlying muscle and grafted it onto 8-to 12-week-old male scid recipient mice. Dressings were removed after 3 weeks. Each animal was photographed weekly.
42. Genomic sequences containing SHH were isolated from a bacterial artificial chromosome library obtained from Research Genetics. Primers used to screen this library from exon 2 [ACC GAG GGC TGG GAC GAA GAT GGC and GCG AGC CAG CAT GCC GTA CTT GCT G (28)] identified BAC 270A17, which was digested with restriction enzymes and ligated with vectorette linkers (29). Exon-intron boundaries for the three exons were determined by sequencing polymerase chain reaction (PCR) products amplified using the universal vectorette primer and SHH cDNA primers selected from published sequences. Since we were unable to obtain sequences from the exon 2-intron 3′ boundary, a primer from the 3′ end of exon 2 was used. Primers used to amplify genomic SHH were as follows: exon 1, CCG CCG CGC GCA CTC G and AAG GAG CGG GTG AAA TCA CC; exon 2, TAA CGT GTC CGT CGG TGG G and TGC TTT CAC CGA GCA GTG G; and exon 3, CCT CCT CCC CGA GAC GC and GGC CCC CTC CCG CGC C. Mutations were identified by single-strand conformation polymorphism (SSCP) analysis of PCR products amplified from genomic DNA. The PCR products were sequenced on both strands directly from the PCR-produced templates and after cloning into Bluescript. Subsequent to our completion of this work, another group has published intron sequences and primers useful for amplifying SHH exons from genomic DNA (26).
43. DNA from one other BCC had a methionine to isoleucine change at position 115, but this change was also present in DNA from the patient's blood. This unusually large BCC was diagnosed at age 40 in a patient with no other phenotypic abnormalities suggestive of BCNS.
44. K. F. Liem, G. Tremmi, H. Roelink, T. M. Jessell, Cell 82, 969 (1995); H. Roelink et al., ibid. 81, 445 (1995); C. Tabin, ibid. 80, 671 (1995); M. J. Cohn and C. Tickle, Trends Genet. 12, 253 (1996).
45. K. F. Liem, G. Tremmi, H. Roelink, T. M. Jessell, Cell 82, 969 (1995); H. Roelink et al., ibid. 81, 445 (1995); C. Tabin, ibid. 80, 671 (1995); M. J. Cohn and C. Tickle, Trends Genet. 12, 253 (1996).
46. K. F. Liem, G. Tremmi, H. Roelink, T. M. Jessell, Cell 82, 969 (1995); H. Roelink et al., ibid. 81, 445 (1995); C. Tabin, ibid. 80, 671 (1995); M. J. Cohn and C. Tickle, Trends Genet. 12, 253 (1996).
47. K. F. Liem, G. Tremmi, H. Roelink, T. M. Jessell, Cell 82, 969 (1995); H. Roelink et al., ibid. 81, 445 (1995); C. Tabin, ibid. 80, 671 (1995); M. J. Cohn and C. Tickle, Trends Genet. 12, 253 (1996).
48. S. Ting-Berreth and C. Chuong, Dev. Dyn. 207, 157 (1996).
49. J. Arbeit, Cancer Surv. 26, 7 (1996).
50. E. Belloni et al., Nature Genet. 14, 353 (1996); E. Roessler et al., ibid., p. 357.
51. E. Belloni et al., Nature Genet. 14, 353 (1996); E. Roessler et al., ibid., p. 357.
52. D. Medalie, J. Invest. Dermatol. 107, 121 (1996).
53. V. Marigo et al., Genomics 28, 44 (1995).
54. J. Riley et al., Nucleic Acid Res. 18, 2887 (1990).
55. Y. Echelard et al., Cell 75, 1417 (1993).
56. L. Goodrich, R. Johnson, L. Milenkovic, J. A. McMahon, M. Scott, Genes Dev. 10, 301 (1996).
57. In situ hybridization studies were performed on mouse embryonic skin with the use of antisense and sense control probes and standard techniques. The Shh template (30) was a mouse Shh partial cDNA missing 300 bp of the 3′ coding region. The ptc template was M2-3, an 841-bp cDNA fragment from the 5′ end of the coding region (31).
58. T. Lufkin et al., Nature 359, 835 (1992).
59. L. Guo, Q.-C. Yu, E. Fuchs, EMBO J. 12, 973 (1993).
60. We thank H. Fan and P. Khavari for instruction in skin grafting techniques and the Scott lab, D. Kingsley, A. McMahon, E. Fuchs, B. Smoller, A. Rothman, J. Xie, and C. Tabin for clones and advice. We thank D. Roop (K14), Z. Liu (BPAG2), J. P. Ortonne (Lam5), and S. Yuspa (K6) for antibodies. A.E.O. was supported by a grant from the National Institute for Arthritis and Musculoskeletal Diseases. Research in San Francisco was supported by NIH grant AR39959. M.P.S. is an Investigator of the Howard Hughes Medical Institute and this research was done with the Institute's support. Human and mouse work was done according to NIH Human Subjects and Animal Use Guidelines at each institution.