The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells.

Alani, Rhoda M.; Brown, Powel H.; Binétruy, Bernard; Dosaka, Hirotoshi; Rosenberg, Richard K.; Angel, Peter; Karin, Michael; Birrer, Michael J.

doi:10.1128/mcb.11.12.6286

Cited by 120 publications

(100 citation statements)

References 52 publications

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“…Blocking AP1 activity using dominant negative cJun or cFos mutants reverts the transformed phenotype of Ras-overexpressed NIH3T3 ®broblasts (Lloyd et al, 1991;Suzuki et al, 1994). A correlation was also observed between Ras transforming e ciency and cJun transcriptional activity (Alani et al, 1991;Westwick et al, 1994). This is consistent with the idea that AP1 complexes containing cJun are essential downstream e ectors of Ras.…”

Section: Introductionsupporting

confidence: 87%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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Section: Introductionsupporting

confidence: 87%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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“…Wild type c-Jun and mutants cloned into either RSV-or CMV-based eukaryotic expression vectors have been previously described: c-Jun/CMV (Brown et al, 1996); c-Jun/RSV ; JunD287 ± 331 (Alani et al, 1991); the leucine zipper point mutants, M8, M9 and M14, ; internal deletion mutants, JunD194 ± 223 and JunD146 ± 221 ; JunA?D 265 In265 (Brown et al, 1996); c-Jun/v-Jun chimeras (Oehler et al, 1993); and cJun Ala63/73 (Smeal et al, 1991). JunB (Schutte et al, 1989) and JunD (Ryder et al, 1989) have been previously described.…”

Section: Plasmidsmentioning

confidence: 99%

Identification of domains of c-Jun mediating androgen receptor transactivation

et al. 1998

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“…Deregulated expression of cJun can lead to malignant transformation of immortalized rat ®broblasts while transformation of primary rat embryo cells required co-expression of an activated c-Ha-ras (Alani et al, 1991;Schutte et al, 1989). In chicken embryo ®broblasts, cJun can induce cellular transformation by itself (Suzuki et al, 1991;Castellazzi et al, 1990).…”

mentioning

confidence: 99%

“…To our knowledge, this is the ®rst reported example of cJun overexpression inducing human cancer cells to form tumors in nude mice. c-jun has been demonstrated to transform primary avian or rodent cells as a single gene or in cooperation with an activated ras gene (Alani et al, 1991;Schutte et al, 1989). The mechanism by which cJun transforms cells remains unclear but presumably involves the regulation of gene expression.…”

mentioning

confidence: 99%

cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype

et al. 1999

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We have previously demonstrated decreased Jun/AP-1 activity in the breast cancer cell line MCF-7 when compared to normal or immortalized mammary epithelial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, which mimic those seen clinically in breast cancer. Overexpression of Jun causes signi®cant alterations in the composition of AP-1, decreased junB and increased fra-1 expression and results in an increased biologic aggressiveness. MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells are unresponsive to the growth stimulating e ects of estrogen and growth inhibitory e ects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells have no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory e ects of estrogen indicating that full-length cJun is required to acquire the estrogenindependent phenotype in breast cancer cells.

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The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells.

Cited by 120 publications

References 52 publications

Transformation by ras modifies AP1 composition and activity

Transformation by ras modifies AP1 composition and activity

Identification of domains of c-Jun mediating androgen receptor transactivation

cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype

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