Disease relevance of Tpm2

• Since Trop2 is undetectable in undifferentiated spindle cell carcinomas, this suggests a preferential expression at early stages of tumor progression [1].
• These results suggest that the suppression of TM2 synthesis is linked to the metastatic potential of Lewis lung carcinoma cells [2].

High impact information on Tpm2

• Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart [3].
• This loss of SKA expression, together with a decrease in beta-tropomyosin expression, contributed to myofiber growth defects, as suggested by the extensive sarcomere disorganization found in mutant muscles [4].
• Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells that express beta-tropomyosin [5].
• Furthermore, suppression of TM2 synthesis was induced in P29 cells during incubation in medium containing dimethyl sulfoxide or butyric acid, which induced the metastatic phenotype of P29 cells [2].
• Integrin alpha6 and two unknown genes were expressed in high-metastatic cells, whereas beta-tropomyosin, macrophage colony-stimulating factor, inhibin/activin betaB subunit, and two unknown genes were expressed in low-metastatic cells [6].

Biological context of Tpm2

• The cloned murine Trop2 gene is functional, as indicated by sequencing and by expression after transfection [1].
• Intriguingly, the cytoplasmic tail of Trop2 shows a highly conserved phosphatidylinositol 4,5-bisphosphate (PIP2)-binding sequence, which overlaps with a protein kinase C phosphorylation site [1].
• Thus, we speculate that PIP2 might regulate the phosphorylation state of Trop2 and play a role in its signal transduction [1].
• Striated muscle-specific alpha-tropomyosin is the predominant isoform in cardiac muscle, with low levels of beta-tropomyosin restricted to fetal development in the mouse [7].
• When expression from the beta-tropomyosin transgene is terminated, alpha-tropomyosin expression returns to normal levels [8].

Anatomical context of Tpm2

• Murine Trop2 mRNA is detected in normal kidney, lung, ovary and testis, similarly to the human gene [1].
• To explore further the significance of altering the alpha- to beta-tropomyosin isoform ratio in developing murine myocardium, we generated transgenic mice which express beta-tropomyosin at high levels in the heart [7].
• To understand the functional role of various tropomyosin isoforms during myofilament activation and regulation in the intact sarcomere, we generated transgenic mice that overexpress striated muscle-specific beta-tropomyosin in the adult heart [7].
• Tropomyosin-2 cDNA lacking the 3' untranslated region riboregulator induces growth inhibition of v-Ki-ras-transformed fibroblasts [9].
• There is a preferential formation of the alpha beta-heterodimer in the transgenic mouse myofibrils, and there are no detectable alterations in the expression of other contractile protein genes, including the endogenous beta-tropomyosin isoform [8].

Associations of Tpm2 with chemical compounds

• Two important charge differences between the alpha- and beta-tropomyosin (TM) isoforms are the exchange of a serine residue in the inner-core region at position 229, and a histidine residue at the carboxy-terminal end at position 276, with glutamic acid and asparagine, respectively [10].
• Compensatory changes in Ca(2+) and myocardial O(2) consumption in beta-tropomyosin transgenic hearts [11].
• T16 and MOv-16 efficiently immunoprecipitate Trop-2 from Trop-2 transfectants and from the human cell line OVCA-432, indicating that it is a cell surface glycoprotein, with an apparent molecular weight of 57 kD in non-reducing conditions [12].

Regulatory relationships of Tpm2

• Rescue of high expression beta-tropomyosin transgenic mice by 5-propyl-2-thiouracil. Regulating the alpha-myosin heavy chain promoter [13].

Other interactions of Tpm2

• Our earlier results succinctly demonstrate that overexpression of beta-tropomyosin in the hearts of transgenic mice decreases endogeneous alpha-tropomyosin levels while altering diastolic function of the myocardium [7].
• This is the first report demonstrating that transcriptional regulatory elements located within the alpha-myosin heavy chain promoter can be manipulated to rescue potentially lethal phenotypes, such as high expression beta-tropomyosin transgenic mice [13].
• The myofibrillar proteins myosin heavy chain, alpha-actin, and alpha- and beta-tropomyosin were identified using antibody reagents and two-dimensional PAGE analysis [14].

Analytical, diagnostic and therapeutic context of Tpm2

• To develop an animal model to study the function of this molecule in vivo, we have cloned the murine Trop2 gene [1].
• Trop-2 is a novel calcium signal transducer expressed at high levels by most human carcinomas [1].
• Using human TROP2 primers, we amplified by PCR a segment of murine Trop2 [1].
• The tropomyosin mRNAs of mouse striated muscles: molecular cloning of beta-tropomyosin [15].
• Since the 162-46.2 mAb works poorly in immunoprecipitation, to characterize the structure of Trop-2 we searched for other mAbs directed against this molecule [12].

References