G Protein-Coupled Receptor Systems Involved in Cell Growth and Oncogenesis

Dhanasekaran, N.; Heasley, Lynn E.; Johnson, Gary L.

doi:10.1210/edrv-16-3-259

Cited by 179 publications

(112 citation statements)

References 0 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…For example, mutationally activated Ga s , referred to as the gsp oncogene (Landis et al, 1989), results in hyperplasia of endocrine cells, and are present in human thyroid and pituitary tumors (reviewed in Dhanasekaran et al, 1995), and in the McCune-Albright syndrome, which exhibits autonomous hyperproliferation in multiple endocrine glands (Weinstein et al, 1991). Activating mutations have also been identi®ed for Ga i2 , referred to as the gip2 oncogene, in a subset of ovarian sex cord stromal tumors and adrenal cortical tumors (Lyons et al, 1990).…”

Section: Oncogenic Potential Of G Protein-coupled Receptorsmentioning

confidence: 99%

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

1998

View full text Add to dashboard Cite

Section: Oncogenic Potential Of G Protein-coupled Receptorsmentioning

confidence: 99%

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

1998

View full text Add to dashboard Cite

“…The constitutive activation of Ras, together with the activation or inactivation of other genes, contributes to uncontrolled cell growth, cell transformation, and the development of human cancer (Dhanasekaran et al, 1995;Fearon, 1997). Moreover, many types of human tumors that do not harbor mutated ras genes may depend on Ras-regulated signal transduction pathways as well as on Ras activators and e ectors.…”

Section: Termination Of Ras E Ector Interactions Involves Rasmentioning

confidence: 99%

A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice

et al. 1999

View full text Add to dashboard Cite

Constitutively active Ras proteins, their regulatory components, and overexpressed tyrosine kinase receptors that activate Ras, are frequently associated with cell transformation in human tumors. This suggests that functional Ras antagonists may have anti-tumor activity. Studies in rodent ®broblasts have shown that S-trans, transfarnesylthiosalicylic acid (FTS) acts as a rather speci®c nontoxic Ras antagonist, dislodging Ras from its membrane anchorage domains and accelerating its degradation. FTS is not a farnesyltransferase inhibitor, and does not a ect Ras maturation. Here we demonstrate that FTS also acts as a functional Ras antagonist in human pancreatic cell lines that express activated KRas (Panc-1 and MiaPaCa-2). In Panc-1 cells, FTS at a concentration of 25 ± 100 mM reduced the amount of Ras in a dose-dependent manner and interfered with serumdependent and epidermal growth factor-stimulated ERK activation, thus inhibiting both anchorage-dependent and anchorage-independent growth of Panc-1 cells in vitro. FTS also inhibited tumor growth in Panc-1 xenografted nude mice, apparently without systemic toxicity. Daily FTS treatment (5 mg/kg intraperitoneally) in mice with tumors (mean volume 0.07 cm 3 ) markedly decreased tumor growth (after treatment for 18 days, tumor volume had increased by only 23+30-fold in the FTStreated group and by 127+66-fold in controls). These ®ndings suggest that FTS represents a new class of functional Ras antagonists with potential therapeutic value.

show abstract

“…Subsequently, these observations led to the investigation of growth altering properties of other G proteins (Gupta et al, 1992a;Pouyssegur and Seuwen, 1992;Dhanasekaran et al, 1995;Dhanasekaran and Vara Prasad, 1998). Growth-promoting activities of di erent Ga-subunits were investigated by expressing the GTPase-de®cient mutants of di erent Ga-subunits in various cell-lines.…”

Section: G Proteins In the Regulation Of Cell Growth And DI Erentiationmentioning

confidence: 99%

“…Although it has been known that G proteins are involved in signal transduction processes ranging from sensory perception to cell-growth regulation, their oncogenic properties have been realized only recently (Gilman, 1987;Johnson and Dhanasekaran, 1989;Dhanasekaran et al, 1995Dhanasekaran and Vara Prasad, 1998). Studies from several laboratories have de®ned the novel mechanisms through which G proteins regulate cell growth, di erentiation, and oncogenesis.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

View full text Add to dashboard Cite

G Proteins provide signal transduction mechanisms to seven transmembrane receptors. Recent studies have indicated that the a-subunits as well as the bg-subunits of these proteins regulate several critical signaling pathways involved in cell proliferation, di erentiation and apoptosis. Of the 17 a-subunits that have been cloned, at least ten of them have been shown to couple mitogenic signaling in ®broblast cells. Activating mutations in Ga s , Ga i2 , and Ga 12 have been correlated with di erent types of tumors. In addition, the ability of the bg-subunits to activate mitogenic pathways in di erent cell-types has been de®ned. The present review brie¯y summarizes the diverse and novel signaling pathways regulated by the a-as well as the bg-subunits of G proteins in regulating cell proliferation.

show abstract

G Protein-Coupled Receptor Systems Involved in Cell Growth and Oncogenesis

Cited by 179 publications

References 0 publications

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice

Regulation of cell proliferation by G proteins

Contact Info

Product

Resources

About