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Mammary Tumors Accelerates Metastases of Transgenic In vivo 1 β Factor Conditional Overexpression of Active Transforming Growth
| Content Provider | Semantic Scholar |
|---|---|
| Author | Muraoka-Cook, Rebecca S. Kurokawa, Hirokazu Koh, Yasuhiro Forbes, James T. Roebuck, L. Renee Barcellos-Hoff, Mary Helen Moody, Susan E. Chodosh, Lewis A. Arteaga, Carlos L. |
| Copyright Year | 2004 |
| Abstract | To address the role of transforming growth factor (TGF) in the progression of established tumors while avoiding the confounding inhibitory effects of TGFon early transformation, we generated doxycycline (DOX)-inducible triple transgenic mice in which active TGF1 expression could be conditionally regulated in mouse mammary tumor cells transformed by the polyomavirus middle T antigen. DOX-mediated induction of TGF1 for as little as 2 weeks increased lung metastases >10-fold without a detectable effect on primary tumor cell proliferation or tumor size. DOX-induced active TGF1 protein and nuclear Smad2 were restricted to cancer cells, suggesting a causal association between autocrine TGFand increased metastases. Antisense-mediated inhibition of TGF1 in polyomavirus middle T antigen–expressing tumor cells also reduced basal cell motility, survival, anchorage-independent growth, tumorigenicity, and metastases. Therefore, induction and/or activation of TGFin hosts with established TGF–responsive cancers can rapidly accelerate metastatic progression. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/64/24/9002.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
