Decreased transforming growth factor β type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression

Tong Zhang, Lillian B. Nanney, Mark O. Peeler, Christopher S. Williams, Laura Lamps, Kathleen J. Heppner, Raymond N. DuBois, R. Daniel Beauchamp

Research output: Contribution to journalArticle

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Abstract

Tumor cells often become resistant to the growth-inhibitory effects of transforming growth factor β (TGF-β). Recent studies have identified TGF- β type II receptor (RII) mutations in a subset of cancers, including colon cancer. To evaluate the expression of TGF-β RII in premalignant intestinal adenomas and the relationship with cell cycle regulation, we investigated the expression of TGF-β RII, cyclin D1, and cyclin-dependent kinase 4 (Cdk4) in Min/+ mouse intestinal adenomas. Immunohistochemistry indicated that TGF-β RII cytoplasmic immunoreactivity was undetectable in the proliferative crypt zones of the normal small intestinal and normal colonic epithelium but was abundant toward the villus tips of the normal small intestine and the lumenal third of the colonic glands. As was observed in the proliferating crypt zones, TGF-β RII immunoreactivity was dramatically decreased or undetectable in all adenomas examined in comparison to the abundant levels in adjacent normal differentiated intestinal epithelium. TGF-β RII mRNA was also reduced in the adenomas in comparison to normal mucosa as determined by reverse transcription-PCR. In an inverse distribution to TGF-β RII, Cdk4 nuclear immunoreactivity was restricted to the crypt regions of the small and large intestine, whereas cyclin D1 immunoreactivity was uniformly absent in normal intestinal epithelium. For both cyclin D1 and Cdk4, protein and mRNA levels were increased in intestinal adenomas but not in normal intestinal epithelium as determined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. In summary, the lack of TGF-β RII expression was associated with increased cyclin D1 and Cdk4 expression in Mini/+ mouse intestinal adenomas. We hypothesize that the former may enable tumor cells to escape from the normal growth-constraining influence of TGF-β, whereas the latter promotes inappropriate cell proliferation and adenoma progression.

Original languageEnglish (US)
Pages (from-to)1638-1643
Number of pages6
JournalCancer Research
Volume57
Issue number9
StatePublished - May 1 1997
Externally publishedYes

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Cyclin-Dependent Kinase 4
Growth Factor Receptors
Cyclin D1
Transforming Growth Factors
Adenoma
Intestinal Mucosa
Colonic Neoplasms
Reverse Transcription
Small Intestine
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA
Large Intestine
Growth
In Situ Hybridization
Neoplasms
Cell Cycle
Mucous Membrane
Epithelium
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhang, T., Nanney, L. B., Peeler, M. O., Williams, C. S., Lamps, L., Heppner, K. J., ... Beauchamp, R. D. (1997). Decreased transforming growth factor β type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. Cancer Research, 57(9), 1638-1643.

Decreased transforming growth factor β type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. / Zhang, Tong; Nanney, Lillian B.; Peeler, Mark O.; Williams, Christopher S.; Lamps, Laura; Heppner, Kathleen J.; DuBois, Raymond N.; Beauchamp, R. Daniel.

In: Cancer Research, Vol. 57, No. 9, 01.05.1997, p. 1638-1643.

Research output: Contribution to journalArticle

Zhang, T, Nanney, LB, Peeler, MO, Williams, CS, Lamps, L, Heppner, KJ, DuBois, RN & Beauchamp, RD 1997, 'Decreased transforming growth factor β type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression', Cancer Research, vol. 57, no. 9, pp. 1638-1643.
Zhang, Tong ; Nanney, Lillian B. ; Peeler, Mark O. ; Williams, Christopher S. ; Lamps, Laura ; Heppner, Kathleen J. ; DuBois, Raymond N. ; Beauchamp, R. Daniel. / Decreased transforming growth factor β type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. In: Cancer Research. 1997 ; Vol. 57, No. 9. pp. 1638-1643.
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abstract = "Tumor cells often become resistant to the growth-inhibitory effects of transforming growth factor β (TGF-β). Recent studies have identified TGF- β type II receptor (RII) mutations in a subset of cancers, including colon cancer. To evaluate the expression of TGF-β RII in premalignant intestinal adenomas and the relationship with cell cycle regulation, we investigated the expression of TGF-β RII, cyclin D1, and cyclin-dependent kinase 4 (Cdk4) in Min/+ mouse intestinal adenomas. Immunohistochemistry indicated that TGF-β RII cytoplasmic immunoreactivity was undetectable in the proliferative crypt zones of the normal small intestinal and normal colonic epithelium but was abundant toward the villus tips of the normal small intestine and the lumenal third of the colonic glands. As was observed in the proliferating crypt zones, TGF-β RII immunoreactivity was dramatically decreased or undetectable in all adenomas examined in comparison to the abundant levels in adjacent normal differentiated intestinal epithelium. TGF-β RII mRNA was also reduced in the adenomas in comparison to normal mucosa as determined by reverse transcription-PCR. In an inverse distribution to TGF-β RII, Cdk4 nuclear immunoreactivity was restricted to the crypt regions of the small and large intestine, whereas cyclin D1 immunoreactivity was uniformly absent in normal intestinal epithelium. For both cyclin D1 and Cdk4, protein and mRNA levels were increased in intestinal adenomas but not in normal intestinal epithelium as determined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. In summary, the lack of TGF-β RII expression was associated with increased cyclin D1 and Cdk4 expression in Mini/+ mouse intestinal adenomas. We hypothesize that the former may enable tumor cells to escape from the normal growth-constraining influence of TGF-β, whereas the latter promotes inappropriate cell proliferation and adenoma progression.",
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AU - Williams, Christopher S.

AU - Lamps, Laura

AU - Heppner, Kathleen J.

AU - DuBois, Raymond N.

AU - Beauchamp, R. Daniel

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