Transforming growth factor β1 (TGFβ1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGFβ1 antisense expression plasmid Journal Article
| Authors: | Huang, F.; Newman, E.; Theodorescu, D.; Kerbel, R. S.; Friedman, E. |
| Article Title: | Transforming growth factor β1 (TGFβ1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGFβ1 antisense expression plasmid |
| Abstract: | A transforming growth factor β1 (TGFβ1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGFβ1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGFβ1 mRNA and active, secreted TGFβ1 protein of the parental line. K6 exhibited no change in TGFβ2 expression, and TGFβ3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent growth and a 3-fold decrease in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen I-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGFβ1. Tumors that did arise from the K6 antisense transfectant cells bad lost antisense TGFβ1 expression and expressed the same TGFβ1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGFβ1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGFβ1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGFβ1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers and Prev., 4: 549-554, 1995). |
| Keywords: | controlled study; nonhuman; liver neoplasms; comparative study; polymerase chain reaction; animal cell; animal; mice; cell survival; cell division; metastasis; transforming growth factor beta; cell line; colonic neoplasms; dna, antisense; tumor cells, cultured; transfection; cancer invasion; gene expression regulation; molecular sequence data; kinetics; mice, nude; rna, messenger; neoplasm metastasis; transplantation, heterologous; transforming growth factor beta1; base sequence; plasmids; gene control; neoplasm invasiveness; dna primers; colon carcinoma; complementary dna; colon carcinogenesis; dna probes; human; priority journal; article; support, u.s. gov't, p.h.s. |
| Journal Title: | Cell Growth & Differentiation |
| Volume: | 6 |
| Issue: | 12 |
| ISSN: | 1044-9523 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1995-12-01 |
| Start Page: | 1635 |
| End Page: | 1642 |
| Language: | English |
| PUBMED: | 9019169 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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