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Oncogene-Mediated Transformation: An In Vitro Model for Colon Carcinogenesis

Oncogene-Mediated Transformation: An In Vitro Model for Colon Carcinogenesis Abstract • Evaluation of molecular events in human colon polyps and tumors has revealed constitutive elevated expression of c-myc, activation of both ras and src proto-oncogenes, and allelic deletion events involving inactivation of putative regulatory genes, including p53.To evaluate the contribution of each of these events to colon carcinogenesis, it is desirable to establish epithelial cell lines representing different stages of neoplastic progression. Such in vitro models can be used to establish a primary role for different genes implicated in neoplastic transformation, identifying events involved in multistep carcinogenesis and delineating the factors modulating cellular transformation. We present herein a summary of such an in vitro model for colon carcinogenesis using the introduction of relevant genetic elements into normal mucosa to identify the molecular steps and accompanying cellular events underlying neoplastic progression in the colon. (Arch Surg. 1991;126:1387-1389) References 1. Bos JL, Fearon ER, Hamilton SR, et al. Prevalence of ras gene mutations in human colorectal cancers . Nature . 1987;327:293-297.Crossref 2. Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis . Nature . 1987;327:298-303.Crossref 3. Erisman MD, Scott JK, Watt RA, Astrim SM. The c-myc protein is constitutively expressed at elevated levels in colorectal carcinoma cell lines . Oncogene . 1988;2:367-378. 4. Fearon EF, Vogelstein B. A genetic model for colorectal tumorigenesis . Cell . 1990;61:759-767.Crossref 5. Bolen JB, Veillette A, Schwartz AM, DeSeau V, Rosen N. Activation of pp60 c-src protein kinase activity in human colon carcinoma . Proc Natl Acad Sci U S A . 1987;84:2251-2255.Crossref 6. Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel M. Analysis of pp60 c-src protein kinase activity in human tumor cell lines and tissues . J Biol Chem . 1986;261:13754-13759. 7. Cartwright CA, Meisler AI, Eckhart W. Activation of pp60 c-src protein kinase is an early event in colonic carcinogenesis . Proc Natl Acad Sci U S A . 1990;87:558-561.Crossref 8. Weinberg RA. Oncogenes, anti-oncogenes and the molecular basis of multistep carcinogenesis . Cancer Res . 1989;49:3713-3721. 9. Parkinson DR, Schnipper LE, Weinberg RA. Cancer biology . In: Cancer Manual . 8th ed. Boston, Mass: American Cancer Society; 1990:28-39. 10. Kedinger M, Haffen K, Simon-Assman PM. Intestinal tissue and cell cultures . Differentiation . 1987;36:71-85.Crossref 11. Quaroni A, Wands J, Trelstad RL, Isselbacher KJ. Epithelioid cell cultures from rat small intestine: characterization by morphologic and immunologic criteria . Cell Biol . 1979;80:248-265.Crossref 12. Emami S, Mir L, Gespach C, Rosselin G. Transfection of fetal rat intestinal epithelial cells by viral oncogenes: establishment and characterization of the E1A immortalized SLC-11 cell line . Proc Natl Acad Sci U S A . 1989;86:3194-3198.Crossref 13. Grinnell F. Cell-collagen interactions: overview . Methods Enzymol . 1982;82:499-503. 14. D'Emilia JC, Mathey-Prevot B, Jaros K, Wolf B, Steele G, Summerhayes IC. Preneoplastic lesions induced by myc and src oncogenes in a heterotopic rat colon . Oncogene . 1991;6:303-309. 15. Wiltz O, O'Hara C, Steele GD, Mercurio AM. Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma, but not for normal colon . Gastroenterology . 1991;100:1266-1278. 16. Ciardello F, McGeady ML, Kim N, et al. Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene but not by the c-neu proto-oncogene and overexpression of the transforming growth factor alpha complementary DNA leads to transformation . Cell Growth Differentiation . 1990;11:407-420. 17. Dotto GP, Weinberg RA, Aziza A. Malignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells . Proc Natl Acad Sci U S A . 1988;85:6389-6393.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Oncogene-Mediated Transformation: An In Vitro Model for Colon Carcinogenesis

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Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1991.01410350077011
Publisher site
See Article on Publisher Site

Abstract

Abstract • Evaluation of molecular events in human colon polyps and tumors has revealed constitutive elevated expression of c-myc, activation of both ras and src proto-oncogenes, and allelic deletion events involving inactivation of putative regulatory genes, including p53.To evaluate the contribution of each of these events to colon carcinogenesis, it is desirable to establish epithelial cell lines representing different stages of neoplastic progression. Such in vitro models can be used to establish a primary role for different genes implicated in neoplastic transformation, identifying events involved in multistep carcinogenesis and delineating the factors modulating cellular transformation. We present herein a summary of such an in vitro model for colon carcinogenesis using the introduction of relevant genetic elements into normal mucosa to identify the molecular steps and accompanying cellular events underlying neoplastic progression in the colon. (Arch Surg. 1991;126:1387-1389) References 1. Bos JL, Fearon ER, Hamilton SR, et al. Prevalence of ras gene mutations in human colorectal cancers . Nature . 1987;327:293-297.Crossref 2. Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis . Nature . 1987;327:298-303.Crossref 3. Erisman MD, Scott JK, Watt RA, Astrim SM. The c-myc protein is constitutively expressed at elevated levels in colorectal carcinoma cell lines . Oncogene . 1988;2:367-378. 4. Fearon EF, Vogelstein B. A genetic model for colorectal tumorigenesis . Cell . 1990;61:759-767.Crossref 5. Bolen JB, Veillette A, Schwartz AM, DeSeau V, Rosen N. Activation of pp60 c-src protein kinase activity in human colon carcinoma . Proc Natl Acad Sci U S A . 1987;84:2251-2255.Crossref 6. Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel M. Analysis of pp60 c-src protein kinase activity in human tumor cell lines and tissues . J Biol Chem . 1986;261:13754-13759. 7. Cartwright CA, Meisler AI, Eckhart W. Activation of pp60 c-src protein kinase is an early event in colonic carcinogenesis . Proc Natl Acad Sci U S A . 1990;87:558-561.Crossref 8. Weinberg RA. Oncogenes, anti-oncogenes and the molecular basis of multistep carcinogenesis . Cancer Res . 1989;49:3713-3721. 9. Parkinson DR, Schnipper LE, Weinberg RA. Cancer biology . In: Cancer Manual . 8th ed. Boston, Mass: American Cancer Society; 1990:28-39. 10. Kedinger M, Haffen K, Simon-Assman PM. Intestinal tissue and cell cultures . Differentiation . 1987;36:71-85.Crossref 11. Quaroni A, Wands J, Trelstad RL, Isselbacher KJ. Epithelioid cell cultures from rat small intestine: characterization by morphologic and immunologic criteria . Cell Biol . 1979;80:248-265.Crossref 12. Emami S, Mir L, Gespach C, Rosselin G. Transfection of fetal rat intestinal epithelial cells by viral oncogenes: establishment and characterization of the E1A immortalized SLC-11 cell line . Proc Natl Acad Sci U S A . 1989;86:3194-3198.Crossref 13. Grinnell F. Cell-collagen interactions: overview . Methods Enzymol . 1982;82:499-503. 14. D'Emilia JC, Mathey-Prevot B, Jaros K, Wolf B, Steele G, Summerhayes IC. Preneoplastic lesions induced by myc and src oncogenes in a heterotopic rat colon . Oncogene . 1991;6:303-309. 15. Wiltz O, O'Hara C, Steele GD, Mercurio AM. Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma, but not for normal colon . Gastroenterology . 1991;100:1266-1278. 16. Ciardello F, McGeady ML, Kim N, et al. Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene but not by the c-neu proto-oncogene and overexpression of the transforming growth factor alpha complementary DNA leads to transformation . Cell Growth Differentiation . 1990;11:407-420. 17. Dotto GP, Weinberg RA, Aziza A. Malignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells . Proc Natl Acad Sci U S A . 1988;85:6389-6393.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Nov 1, 1991

References