Colon cancer cells that are not growth inhibited by TGF-beta lack functional type I and type II TGF-beta receptors.

Abstract:

OBJECTIVE:The authors determined the molecular mechanisms for the failure of transforming growth factor-beta (TGF-beta) to inhibit the growth of SW1116 and SW48 colon cancer cell lines. BACKGROUND:Transforming growth factor-beta is a bifunctional regulator of cell growth that typically stimulates proliferation of mesenchymal cells, but inhibits proliferation of normal epithelial cells. In the colon, TGF-beta appears to arrest proliferation of enterocytes as they leave the intestinal crypt and move to the villus tip. Transforming growth factor-beta actions are mediated by binding to heteromeric complexes of type I and type II TGF-beta receptors. Loss of TGF-beta responsiveness may contribute to uncontrolled cell growth and cancer. METHODS:The effects of TGF-beta 1 on DNA synthesis were measured by incorporation of tritiated thymidine into DNA of cultures of moderately differentiated adenocarcinoma (SW48) and poorly differentiated adenocarcinoma (SW1116) colon cell lines and a mink lung epithelial cell line (CCL-64). The effects of TGF-beta on the expression of c-myc, TGF-alpha, and TGF-beta in SW48 cells, SW1116 cells, and CCL-64 cells (c-myc only) were measured by Northern blot analysis. Expression of TGF-beta receptors in the cell lines was measured using competitive binding assays, receptor affinity labelling techniques, and reverse transcriptase-polymerase chain reaction. RESULTS:Incubation with TGF-beta 1 (50 ng/mL) did not decrease serum-stimulated uptake of [3H]-thymidine into actively growing cultures of SW48 or SW1116 cells, but suppressed DNA synthesis of actively growing CCL-64 cells by 90%. Similarly, incubation with TGF-beta 1 (12 ng/mL) for 4 hours did not substantially alter the mRNA levels of c-myc, TGF-alpha, and TGF-beta 1 in either colon tumor cell line, although levels of c-myc mRNA in CCL-64 cells were reduced by TGF-beta 1 treatment. Competitive displacement of [125I]-TGF-beta 1 binding detected high levels (16,500 TGF-beta receptors per cell) of specific, high-affinity (200 pmol/L half-displacement) TGF-beta receptors on CCL-64 cells. In marked contrast, very low levels of TGF-beta 1 binding to SW1116 cells (250 receptors per cell) and SW48 cells (260 receptors per cell) were detected. Autoradiograms of CCL-64 cells affinity labelled with [125I]TGF-beta 1 revealed the presence of type I, type II, and type III TGF-beta receptors. No TGF-beta receptors were identified on SW1116 cells, and only very low levels of the nonsignaling type III TGF-beta receptors were detected on SW48 cells. Reverse transcriptase-polymerase chain reaction amplification detected mRNAs for type I, type II, and type III TGF-beta receptors in CCL-64 cells. SW48 cells, and SW1116 cells. CONCLUSIONS:These results suggest that the lack of growth inhibition by TGF-beta in SW48 and SW1116 colon cancer cells may be caused by a lack of expression of functional TGF-beta receptors.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

MacKay SL,Yaswen LR,Tarnuzzer RW,Moldawer LL,Bland KI,Copeland EM 3rd,Schultz GS

doi

10.1097/00000658-199506000-00015

subject

Has Abstract

pub_date

1995-06-01 00:00:00

pages

767-76; discussion 776-7

issue

6

eissn

0003-4932

issn

1528-1140

journal_volume

221

pub_type

杂志文章
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    authors: Busuttil RW,Shaked A,Millis JM,Jurim O,Colquhoun SD,Shackleton CR,Nuesse BJ,Csete M,Goldstein LI,McDiarmid SV

    更新日期:1994-05-01 00:00:00

  • Molecules, cancer, and the surgeon. A review of molecular biology and its implications for surgical oncology.

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    authors: Arbeit JM

    更新日期:1990-07-01 00:00:00

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    authors: Lemmer JH,Strodel WE,Knol JA,Eckhauser FE

    更新日期:1983-07-01 00:00:00

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    更新日期:2004-11-01 00:00:00

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    更新日期:2015-02-01 00:00:00

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    更新日期:2017-07-01 00:00:00

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    更新日期:2019-09-01 00:00:00

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    pub_type: 杂志文章,多中心研究

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    pub_type: 杂志文章

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    更新日期:1980-01-01 00:00:00

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    更新日期:2007-07-01 00:00:00

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    pub_type: 杂志文章,评审

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