A kinase-defective transforming growth factor-beta receptor type II is a dominant-negative regulator for human breast carcinoma MCF-7 cells. 1998

Y Ko, and K M Koli, and S S Banerji, and W Li, and E Zborowska, and J K Willson, and M G Brattain, and C L Arteaga
Department of Biochemistry and Molecular Biology, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008, USA.

The role of transforming growth factor (TGF)-beta type II receptor (T beta RII) in TGF-beta resistance and tumor progression is now well recognized. To test the effects of T beta RII loss in determining malignancy, we transfected a T beta RII-expressing, TGF-beta-sensitive, MCF-7 cell strain (ME24) with a tetracycline-repressible truncated T beta RII (kdT beta RII) construct lacking the cytoplasmic domain of the receptor. Transfection of kdT beta RII into parental ME24 cells (designated ME24t6 after transfection) resulted in high expression levels of kdT beta RII mRNA and cell surface protein which were reversible by tetracycline treatment. ME24t6 cells did not respond to exogenous TGF-beta 1 as measured by inhibition of proliferation or fibronectin (FN) induction, indicating that the truncated T beta RII acted as a dominant-negative inhibitor of both the growth inhibitory and extracellular matrix (ECM) stimulatory TGF-beta effects. Furthermore, inhibition of kdT beta RII expression by tetracycline treatment led to TGF-beta 1-mediated cell growth arrest in the G1 phase of cell cycle and to the accumulation of the hypophosphorylated form of retinoblastoma (Rb) protein. However, compared to parental ME24 cells, transfectants failed to show increased tumorigenicity, indicating that loss of T beta RII itself is not sufficient to account for differences in the malignant properties of T beta RII-expressing and non-expressing MCF-7 cell strains.

UI MeSH Term Description Entries
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077294 Receptor, Transforming Growth Factor-beta Type II A transmembrane serine-threonine kinase that forms a heteromeric complex with TYPE I TGF-BETA RECEPTORS when bound to TGF-BETA. This receptor complex regulates a variety of physiological and pathological processes including CELL CYCLE ARREST; CELL PROLIFERATION; CELL DIFFERENTIATION; WOUND HEALING; EXTRACELLULAR MATRIX production, immunosuppression and ONCOGENESIS. TGF-beta Type II Receptor,TGF-beta Type II Receptors,TGFBR2,TbetaR-II Kinase,Transforming Growth Factor-beta Type II Receptor,Transforming Growth Factor-beta Type II Receptors,Type II TGF-beta Receptor,Type II TGF-beta Receptors,Kinase, TbetaR-II,Receptor, Transforming Growth Factor beta Type II,TGF beta Type II Receptor,TGF beta Type II Receptors,TbetaR II Kinase,Transforming Growth Factor beta Type II Receptor,Transforming Growth Factor beta Type II Receptors,Type II TGF beta Receptor,Type II TGF beta Receptors
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012259 Ribonuclease, Pancreatic An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5. RNase A,Ribonuclease A,Pancreatic RNase,RNase I,Ribonuclease (Pancreatic),Ribonuclease I,Pancreatic Ribonuclease,RNase, Pancreatic
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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