Na(+)-I- symport activity is present in membrane vesicles from thyrotropin-deprived non-I(-)-transporting cultured thyroid cells.

Kaminsky, Stephen M.; Levy, Orlie; Salvador, Carolina; Dai, Ge; Carrasco, Nancy

doi:10.1073/pnas.91.9.3789

Cited by 89 publications

(73 citation statements)

References 34 publications

(27 reference statements)

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“…The e ects of Ras transformation on Pax-8 expression have not yet been reported, although reduced levels of Pax-8 expression have been observed in follicular adenomas (Heldin and Westermark, 1991) and in thyroid cells expressing mutated p53 (Battista et al, 1995). RasC40-dependent signals might also downregulate the expression and/or activity of a recently described novel thyroid transcription factor involved in the regulation of NIS expression (Ohmori et al, 1998), or could a ect NIS activity through a post-transcriptional mechanism similar to that observed for TSH (Kaminsky et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Ras signaling through PI3K confers hormone-independent proliferation that is compatible with differentiation

Cass

Meinkoth

2000

Oncogene

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Hormones are specialized mitogens that stimulate proliferation in their di erentiated target cells. Thyrotropin (TSH), the physiologic regulator of thyroid cells, stimulates cAMP-mediated proliferation and thyroidspeci®c gene expression. The mitogenic e ects of TSH require Ras, therefore Ras activation should be compatible with the maintenance of thyroid di erentiation. However, expression of activated Ras extinguishes the di erentiated phenotype of thyroid cells. One explanation for this apparent paradox is the selective utilization of Ras e ector pathways. We tested the hypothesis that Ras signaling through PI3K mediates the mitogenic e ects of TSH in cells which retain their di erentiated character. Expression of a Ras e ector mutant (RasV12S35) that signals preferentially through Raf-1, although su cient to confer TSH-independent proliferation, abolished hormone-regulated expression of thyroglobulin and the sodium/iodide symporter. In contrast, expression of a Ras mutant (RasV12C40) that binds selectively to PI3K conferred TSH-independent proliferation without marked e ects on thyroid-speci®c gene expression. Unlike the inhibitory e ects of TSH on the proliferation of RasV12S35-expressing cells, TSH enhanced RasV12C40-stimulated proliferation by further increasing the activity of p70s6k, an important mediator of the mitogenic e ects of TSH and RasV12C40. These results demonstrate that channeling Ras-dependent signals to PI3K confers TSH with the ability to stimulate proliferation in di erentiated cells. Oncogene (2000) 19, 924 ± 932.

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Section: Discussionmentioning

confidence: 99%

Ras signaling through PI3K confers hormone-independent proliferation that is compatible with differentiation

Cass

Meinkoth

2000

Oncogene

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“…In tissues expressing mature hNIS and showing the classical basolateral plasma membrane staining, intracellular hNIS immunoreactivity was also found; it would correspond to hNIS in the course of synthesis and trafficking toward and from the plasma membrane. 21,22 It is noteworthy that the observations made on hypofunctioning tumors applied in all respects to nonstimulated NT. Indeed, nonstimulated NT samples from patients under T 4 treatment contained hNIS transcripts and only low amounts of nonglycosylated hNIS.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Trouttet-Masson

Selmi-Ruby

Bernier-Valentin

et al. 2004

The American Journal of Pathology

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“…However, significant iodide uptake is observed only in follicle-forming thyrocytes, indicating the importance of cell polarization and spatial organization for functional activity of NIS [45]. Kaminsky et al (1994) reported persistent NIS activity in membrane vesicles prepared from FRTL-5 cells following prolonged TSH withdrawal. Interestingly, no such activity was detected in intact cells in similar conditions [46].…”

Section: Post-transcriptional Regulation Of Nismentioning

confidence: 99%

“…Kaminsky et al (1994) reported persistent NIS activity in membrane vesicles prepared from FRTL-5 cells following prolonged TSH withdrawal. Interestingly, no such activity was detected in intact cells in similar conditions [46]. This could be explained by the differential cellular expression of NIS following TSH deprivation.…”

Section: Post-transcriptional Regulation Of Nismentioning

confidence: 99%

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

Hingorani¹

2010

CCDT

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The sodium iodide symporter (NIS) is responsible for thyroidal, salivary, gastric, intestinal and mammary iodide uptake. It was first cloned from the rat in 1996 and shortly thereafter from human and mouse tissue. In the intervening years, we have learned a great deal about the biology of NIS. Detailed knowledge of its genomic structure, transcriptional and post-transcriptional regulation and pharmacological modulation has underpinned the selection of NIS as an exciting approach for targeted gene delivery. A number of in vitro and in vivo studies have demonstrated the potential of using NIS gene therapy as a means of delivering highly conformal radiation doses selectively to tumours. This strategy is particularly attractive because it can be used with both diagnostic ( 99m Tc, 125 I, 124 I) and therapeutic ( 131 I, 186 Re, 188 Re, 211 At) radioisotopes and it lends itself to incorporation with standard treatment modalities, such as radiotherapy or chemoradiotherapy. In this article, we review the biology of NIS and discuss its development for gene therapy.

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Na(+)-I- symport activity is present in membrane vesicles from thyrotropin-deprived non-I(-)-transporting cultured thyroid cells.

Cited by 89 publications

References 34 publications

Ras signaling through PI3K confers hormone-independent proliferation that is compatible with differentiation

Ras signaling through PI3K confers hormone-independent proliferation that is compatible with differentiation

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

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