Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene.
S D Markowitz, … , M Swiriduk, J K Willson
S D Markowitz, … , M Swiriduk, J K Willson
Published March 1, 1994
Citation Information: J Clin Invest. 1994;93(3):1005-1013. https://doi.org/10.1172/JCI117048.
View: Text | PDF
Research Article Article has an altmetric score of 6

A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene.

  • Text
  • PDF
Abstract

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.

Authors

S D Markowitz, L Myeroff, M J Cooper, J Traicoff, M Kochera, J Lutterbaugh, M Swiriduk, J K Willson

×

Total citations by year

Year: 2017 2016 2013 2012 2011 2010 2008 2007 2005 2004 2003 2002 2000 1999 1998 1997 1996 1995 1982 Total
Citations: 2 1 1 1 2 1 2 2 3 1 2 2 3 2 4 2 9 6 1 47
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (47)

Title and authors Publication Year
Black Raspberries Enhance Natural Killer Cell Infiltration into the Colon and Suppress the Progression of Colorectal Cancer
P Pan, S Kang, Y Wang, K Liu, K Oshima, YW Huang, J Zhang, M Yearsley, J Yu, LS Wang
Frontiers in immunology 2017
Prognostic value of loss of heterozygosity and sub-cellular localization of SMAD4 varies with tumor stage in colorectal cancer
X Jia, C Shanmugam, RK Paluri, NC Jhala, MP Behring, VR Katkoori, SP Sugandha, S Bae, T Samuel, U Manne
Oncotarget 2017
Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid
A Hulikova, N Black, LT Hsia, J Wilding, WF Bodmer, P Swietach
Proceedings of the National Academy of Sciences 2016
Cholesterol affects gene expression of the Jun family in colon carcinoma cells using different signaling pathways
EJ Scheinman, R Rostoker, D LeRoith
Molecular and Cellular Endocrinology 2013
RET is a potential tumor suppressor gene in colorectal cancer
Y Luo, KD Tsuchiya, DI Park, R Fausel, S Kanngurn, P Welcsh, S Dzieciatkowski, J Wang, WM Grady
Oncogene 2012
Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal-type adenocarcinoma. A tissue microarray analysis of 62 cases
A Franchi, A Palomba, C Fondi, L Miligi, M Paglierani, M Pepi, M Santucci
Histopathology 2011
Advances in Cancer Research
M Lemaire, S Deleu, ED Bruyne, EV Valckenborgh, E Menu, K Vanderkerken
Advances in Cancer Research Volume 110 2011
TNF-related apoptosis-inducing ligand cooperates with NSAIDs via activated Wnt signalling in (pre)malignant colon cells
DM Heijink, M Jalving, D Oosterhuis, IA Sloots, R Koster, H Hollema, JH Kleibeuker, JJ Koornstra, EG de Vries, S Jong
The Journal of Pathology 2010
The aberrant methylation ofTSP1suppresses TGF-β1 activation in colorectal cancer
A Rojas, S Meherem, YH Kim, MK Washington, JE Willis, SD Markowitz, WM Grady
International Journal of Cancer 2008
Chemopreventive Effects of Flax Seed Oil and Flax Seed Meal on Azoxymethane-Induced Colon Tumors in Fisher 344 Male Rats
DS Williams, M Verghese, LT Walker, J Boateng, LA Shackelford, M Guyton, J Jones, J Khatiwada, CB Chawan
International Journal of Cancer Research 2008
Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR-mediated Akt and ERK signal transduction
HY Oh, EJ Lee, S Yoon, BH Chung, KS Cho, SJ Hong
The Prostate 2007
Molecular Prognostic Markers in Locally Advanced Colon Cancer
G Lurje, W Zhang, HJ Lenz
Clinical Colorectal Cancer 2007
The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells
QB She, DB Solit, Q Ye, KE O'Reilly, J Lobo, N Rosen
Cancer Cell 2005
Macrophage Migration Inhibitory Factor Promotes Intestinal Tumorigenesis
JM Wilson, PL Coletta, RJ Cuthbert, N Scott, K MacLennan, G Hawcroft, L Leng, JB Lubetsky, KK Jin, E Lolis, F Medina, JA Brieva, R Poulsom, AF Markham, R Bucala, MA Hull
Gastroenterology 2005
Proliferation and Cdk4 expression in microsatellite unstable colon cancers withTGFBR2 mutations
WM Grady, JE Willis, P Trobridge, J Romero-Gallo, N Munoz, J Olechnowicz, K Ferguson, S Gautam, SD Markowitz
International Journal of Cancer 2005
Colorectal cancer: modeling causes, prevention and therapy
B Marian
Drug Discovery Today: Disease Models 2004
Characterization of the human polymeric immunoglobulin receptor(PIGR) 3'UTR and differential expression ofPIGR mRNA during colon tumorigenesis
JL Traicoff, L Marchis, BL Ginsburg, RE Zamora, NH Khattar, VJ Blanch, S Plummer, SA Bargo, DJ Templeton, G Casey, CS Kaetzel
Journal of Biomedical Science 2003
Reconstitution of TGF-β sensitivity in the VACO-411 human colon carcinoma line by somatic cell fusion with MCF-7
JL Traicoff, S Periyasamy, MG Brattain, W Grady, G Casey
Journal of Biomedical Science 2003
In vitro models for the identification and characterization of tumor-promoting and protective factors for colon carcinogenesis
B Marian
Food and Chemical Toxicology 2002
Early loss of deleted in colorectal carcinoma gene transcript detected in a group of benign colon adenomas
J une L Traicoff, James K V Willson, Sanford D Markowitz
Journal of Biomedical Science 2002
Endocervical Cancer Is Associated with an Increase in the Ligands and Receptors for Transforming Growth Factor-β and a Contrasting Decrease in p27Kip1
J Farley, K Gray, L Nycum, M Prentice, MJ Birrer, SB Jakowlew
Gynecologic Oncology 2000
Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice
F Okada, T Kawaguchi, H Habelhah, T Kobayashi, H Tazawa, N Takeichi, T Kitagawa, M Hosokawa
Laboratory Investigation 2000
TGF-β receptors and DNA repair genes, coupled targets in a pathway of human colon carcinogenesis
S Markowitz
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2000
TGF-β and cancer
M Reiss
Microbes and Infection 1999
Characterization of MAD2B and Other Mitotic Spindle Checkpoint Genes
DP Cahill, LT da Costa, EB Carson-Walter, KW Kinzler, B Vogelstein, C Lengauer
Genomics 1999
Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes
K Takaku, M Oshima, H Miyoshi, M Matsui, MF Seldin, MM Taketo
Cell 1998
Transforming Growth Factor-Beta Expression in Mouse Lung Carcinogenesis
SB Jakowlew, TW Moody, L You, JM Mariano
Experimental Lung Research 1998
Liver Growth and Repair
A Strain, AM Diehl
1998
DNA Damage and Repair: Volume 2: DNA Repair in Higher Eukaryotes
JA Nickoloff, MF Hoekstra
1998
Carbohydrate antigens aberrantly expressed in colorectal carcinoma
Y Matsushita, S Yonezawa, S Nakamori, T Irimura, E Sato
Critical Reviews in Oncology/Hematology 1997
TGF-β receptor signaling
R Derynck, XH Feng
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1997
Defects of TGF-β receptor signaling in mammary cell tumorigenesis
MG Brattain, Y Ko, SS Banerji, G Wu, JK Willson
Journal of Mammary Gland Biology and Neoplasia 1996
Loss of responsiveness to transforming growth factor β (TGFβ) is tightly linked to tumorigenicity in a model of thyroid tumour progression
JP Blaydes, D Wynford-Thomas
International Journal of Cancer 1996
Transforming growth factor-β receptors: Role in physiology and disease
DH Kim, SJ Kim
Journal of Biomedical Science 1996
Maintenance of growth factor signaling through Ras in human colon carcinoma cells containing K-ras mutations
A Buard, PA Zipfel, RS Frey, KM Mulder
International Journal of Cancer 1996
Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas
C Hanski, F Tiecke, M Hummel, ML Hanski, D Ogorek, A Rolfs, A Schmitt-Gräff, H Stein, EO Riecken
Cancer Letters 1996
Effect of partial liver resection on tumour growth
KP de Jong, MJ Slooff, EG de Vries, MA Brouwers, OT Terpstra
Journal of Hepatology 1996
Transforming growth factor-β in GI neoplasia, wound healing and immune response
M Pignatelli, CJ Gilligan
Bailliere's Clinical Gastroenterology 1996
The somatic mutation frequency of the transforming growth factor β receptor type II gene varies widely among different cancers with microsatellite instability
T Abe, H Ouyang, T Migita, Y Kato, M Kimura, K Shiiba, M Sunamura, S Matsuno, A Horii
European Journal of Surgical Oncology (EJSO) 1996
Reduced Expression of Transforming Growth Factor β Type I Receptor Contributes to the Malignancy of Human Colon Carcinoma Cells
J Wang, W Han, E Zborowska, J Liang, X Wang, JK Willson, LZ Sun, MG Brattain
The Journal of biological chemistry 1996
Transforming growth factor $beta; and cancer
P Norgaard, S Hougaard, HS Poulsen, M Spang-Thomsen
Cancer Treatment Reviews 1995
The effect of partial hepatectomy on tumor growth in rats:In vivo andin vitro studies
KP de Jong, HE Lont, AM Bijma, MA Brouwers, EG de Vries, ML van Veen, RL Marquet, MJ Slooff, OT Terpstra
Hepatology 1995
Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2
M Tsujii, RN DuBois
Cell 1995
Is mucinous carcinoma of the colorectum a distinct genetic entity?
C Hanski
British Journal of Cancer 1995
Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability
S Markowitz, J Wang, L Myeroff, R Parsons, L Sun, J Lutterbaugh, RS Fan, E Zborowska, KW Kinzler, B Vogelstein
Science 1995
Demonstration That Mutation of the Type II Transforming Growth Factor beta Receptor Inactivates Its Tumor Suppressor Activity in Replication Error-positive Colon Carcinoma Cells
L Sun
Clinical cancer research 1995
Hormones and Cancer
WW Leavitt
Hormones and Cancer 1982

← Previous 1 2 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 4 patents
15 readers on Mendeley
See more details