Tropomyosin isoform switching in tumorigenic human fibroblasts.

Leavitt, John; Latter, G; Lutomski, L; Goldstein, David J.; Burbeck, Stephen

doi:10.1128/mcb.6.7.2721

Cited by 90 publications

(76 citation statements)

References 28 publications

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“…These cells also exhibit abnormal expression of the tropomyosin isoforms (11). We have now found that, after introduction and expression of functional (-or -y-actin gene clones in HuT-14T cells, we can alter the ,IBy actin synthesis ratios to greater degrees than in the cell lines previously studied, which have all of their normal actin alleles.…”

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confidence: 65%

“…This abundant expression of the transfected mutant 1B-actin gene also resulted in changes in cell morphology and concomitant reduction of rates of synthesis of five of six tropomyosin isoforms (12,13 transformation of avian, rodent, and human fibroblasts (1,2,5,11,15). Furthermore, abundant expression of mutant (-actin in immortalized, nontumorigenic human HuT-12 fibroblasts led to stable tumorigenic conversion of a subpopulation of transfected cells which exhibited enhanced mutant ,B-actin synthesis (13).…”

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confidence: 99%

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Modulation of microfilament protein composition by transfected cytoskeletal actin genes.

Ng¹,

Erba²,

Latter³

et al. 1988

Mol. Cell. Biol.

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HuT-14T is a highly tumorigenic fibroblast cell line which exhibits a reduced steady-state level of beta-actin due to coding mutations in one of two beta-actin alleles. The normal rate of total actin synthesis could be restored in some clones of cells following transfection of the functional beta-actin gene but not following transfection of the functional gamma-actin gene. In gamma-actin gene-transfected substrains that have increased rates of gamma-actin synthesis, beta-actin synthesis is further reduced in a manner consistent with an autoregulatory mechanism, resulting in abnormal ratios of actin isoforms. Thus, both beta- and gamma-actin proteins can apparently regulate the synthesis of their coexpressed isoforms. In addition, decreased synthesis of normal beta-actin seems to correlate with a concomitant down-regulation of tropomyosin isoforms.

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confidence: 65%

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confidence: 99%

Modulation of microfilament protein composition by transfected cytoskeletal actin genes.

Ng¹,

Erba²,

Latter³

et al. 1988

Mol. Cell. Biol.

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“…For example, suppression of high M r TMs, viz., isoforms 1 and 2 (TM1 and TM2, respectively), is nearly universal in all the transformed cell lines tested, while elevated levels of the low M r species such as TM4 and TM5 are reported in some malignant cell types (Bhattacharya et al, 1990;Cooper et al, 1985Cooper et al, , 1987Hendricks and Weintraub, 1981;Leavitt et al, 1986;Matsumura et al, 1983). Although all TMs bind to actin with varying binding a nities, the precise function of each of the isoforms remains largely unknown.…”

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confidence: 99%

Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway

et al. 2001

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Tropomyosin (TM) family of cytoskeletal proteins is implicated in stabilizing actin micro®laments. Many TM isoforms, including tropomyosin-1 (TM1), are downregulated in transformed cells. Previously we demonstrated that TM1 is a suppressor of the malignant transformation, and that TM1 reorganizes micro®la-ments in the transformed cells. To investigate how TM1 induces micro®lament organization in transformed cells, we utilized ras-transformed NIH3T3 (DT) cells, and those transduced to express TM1, and/or TM2. Enhanced expression of TM1 alone, but not TM2, results in re-emergence of micro®laments; TM1, together with TM2 remarkably improves micro®lament architecture. TM1 induced cytoskeletal reorganization involves an enhanced expression of caldesmon, but not vinculin, aactinin, or gelsolin. In addition, TM1-induced cytoskeletal reorganization and the revertant phenotype appears to involve re-activation of RhoA controlled pathways in DT cells. RhoA expression, which is suppressed in DT cells, is signi®cantly increased in TM1-expressing cells, without detectable changes in the expression of Rac or Cdc42. Furthermore, expression of a dominant negative Rho kinase, or treatment with Y-27632 disassembled micro®laments in normal NIH3T3 and in TM1 expressing cells. These data suggest that reactivation of Rho kinase directed pathways are critical for TM1-mediated micro®lament assemblies. Oncogene (2001) 20, 2112 ± 2121.

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“…In non-muscle cells, the role of tropomyosins is less clearly understood, and it is generally thought that they are involved in stabilization of actin microfilaments which, in turn, play an important role in maintaining cell shape, motil-ity, and interaction with extracellular supporting elements (Pollard et al, 1976;CBtC, 1983;Stossel et al, 1985). The terminology of tropomyosins used in this study is one in general use for tropomyosins expressed in fibroblasts (Leavitt et al, 1986). Tropomyosins-1-3 correspond, in increasing order of electrophoretic mobility, to the high-Mr tropomyosins (284 amino acids), which are homologous to tropomyosins expressed in muscle cells, while tropomyosin-4 and tropomyosin-5 correspond to the low-M, tropomyosins (247 or 248 amino acids) characteristic of non-muscle cells.…”

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confidence: 99%

“…The reader is also referred to footnote 2 of Lehrer and Qian (1990) regarding the terminology of smooth muscle tropomyosins. A number of studies have shown that down-regulation of expression of the high-M, tropomyosin isoforms consistently accompanies neoplastic transformation of murine and avian fibroblasts by a variety of retroviral oncogenes, chemical mutagens and transforming growth factors (Hendricks and Weintraub, 1981;Leonardi et al, 1982;Matsumura et al, 1983;Hendricks and Weintraub, 1984;Cooper et al, 1985Cooper et al, , 1987Leavitt et al, 1986). These findings have led to the proposal that deficiency of tropomyosin expression may be a causal biochemical event in neoplastic transforma-tion by many modalities, acting to destabilize the actin microfilaments (Cooper et al, 1985).…”

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confidence: 99%

Expression, Cytoskeletal Utilization and Dimer Formation of Tropomyosin Derived from Retroviral‐Mediated cDNA Transfer

Prasad

Fuldner

Braverman

et al. 1994

European Journal of Biochemistry

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Expression of the tropomyosin-1 isoform was enhanced by cDNA transfer in non-transformed murine 3T3 fibroblasts and also in v-Ki-ras transformed fibroblasts in which native tropomyosin-1 expression had been reduced and tropomyosin-2 synthesis virtually eliminated by action of the oncogene. The level of synthesis of insert-derived tropomyosin-1 was similar in normal and transformed transductants (3 -5 times normal levels). The high level of insert-derived tropomyosin-1 expression resulted in a considerable increase in tropomyosin-1 utilization in the cytoskeleton of transformed cells, but this expression still did not reach normal levels, suggesting an oncogenerelated inhibition of tropomyosin utilization. A large proportion of newly synthesized native tropomyosin-1 in normal, unmodified fibroblasts appeared in homodimers which, upon prolonged incubation, were largely converted to the heterodimers. Excess tropomyosin-1 derived from the inserted cDNA also appeared largely as the homodimer in both normal and transformed cells. This homodimer was utilized effectively in the formation of cytoskeletal structures but was partially converted to heterodimer by chain exchange. Under steady-state conditions, approximately 33 % of the cytoskeletal tropomyosin-1 -containing dimers were homodimers, compared to approximately 10% in normal fibroblasts. The results show that the increased amount of tropomyosin-1 homodimer entering the cytoskeleton under conditions of tropomyosin-1 excess, results in an atypical microfilament composition. The effect of this excess of tropomyosin-1 homodimers on stability or function of microfilament fibers remains to be determined. The results also confirm that the mechanisms of rapid homodimer formation with conversion to heterodimers by chain exchange, known from in vitro studies, also occur in vivo.

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Tropomyosin isoform switching in tumorigenic human fibroblasts.

Cited by 90 publications

References 28 publications

Modulation of microfilament protein composition by transfected cytoskeletal actin genes.

Modulation of microfilament protein composition by transfected cytoskeletal actin genes.

Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway

Expression, Cytoskeletal Utilization and Dimer Formation of Tropomyosin Derived from Retroviral‐Mediated cDNA Transfer

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