Suppression of the Progression Phenotype in Somatic Cell Hybrids Occurs in the Absence of Altered Adenovirus Type 5 Gene Expression

2000

Oncogene

Cancer is a progressive disease in which a tumor cell temporally develops qualitatively new transformation related phenotypes or a further elaboration of existing transformation associated properties. Subtraction hybridization identi®ed a novel gene associated with transformation progression in mutant adenovirus type 5, H5ts125, transformed rat embryo cells, progression elevated gene-3 (PEG-3). To de®ne the mechanism by which expression of PEG-3 is enhanced as a function of cancer progression a 5'-¯anking promoter region of *2.0-kb, PEG-Prom, was isolated, cloned and characterized. The full-length and various mutated regions of the PEG-Prom were linked to a luciferase reporter construct and evaluated for promoter activity during cancer progression. These assays demonstrate a requirement for AP1 and PEA3 sites adjacent to the TATA box region of PEG-3 in mediating basal promoter activity and the enhanced expression of PEG-3 in progressed H5-ts125-transformed rat embryo cells. An involvement of AP1 and PEA3 in PEG-3 regulation was also con®rmed by electrophoretic mobility shift assays (EMSA) and transfection studies with cJun and PEA3 expression vectors. Our ®ndings document the importance of both AP1 and PEA3 transcription factors in mediating basal and elevated expression of PEG-3 in H5ts125-transformed rat embryo cells displaying an aggressive and progressed cancer phenotype. Oncogene (2000) 19, 3411 ± 3421.

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Shi

2000

Oncogene

Subtraction hybridization identifies a transformation progression-associated gene PEG -3 with sequence homology to a growth arrest and DNA damage-inducible gene

Shi

Proc. Natl. Acad. Sci. U.S.A.

1997

Biochemistry. In the article ''Identification by mass spectrometry of the phosphorylated residue responsible for activation of the catalytic domain of myosin I heavy chain kinase, a member of the PAK͞STE20 family'' by Joanna Szczepanowska, Xiaolong Zhang, Christopher J. Herring, Jun Qin, Edward D. Korn, and Hanna Brzeska, which appeared in number 16, August 5, 1997, of Proc. Natl. Acad. Sci. USA (94,(8503)(8504)(8505)(8506)(8507)(8508), the authors wish to note that in Fig. 3, the ions of m͞z 1345.3 and 1247.1 were incorrectly identified as b 13 and b 13 ⌬ , respectively, produced by cleavage of the peptide AS(Pi)VVGTTYW-MAPEVVK between E and V (Fig. 3 Inset). In fact, these ions are b 12 and b 12 ⌬ , produced by cleavage of the peptide between P and E. This correction has no effect on the conclusion that the phosphorylated residue is serine. Also, in Table 2, reference numbers 22-24 should be 21-23 (the reference in the legend is cited correctly) and the MIHCK sequence is from residue 624 to residue 638.Cell Biology. In the article ''Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damageinducible gene'' by Zao

Antisense inhibition of the PTI-1 oncogene reverses cancer phenotypes

Goldstein

Proc. Natl. Acad. Sci. U.S.A.

1998

The genetic alterations and molecular events mediating human prostate cancer development and progression remain to be defined. Rapid expression cloning and differential RNA display detect a putative oncogene, prostate tumor-inducing gene 1 (PTI-1), that is differentially expressed in human prostate (as well as breast, colon, and small cell lung) cancer cell lines, patient-derived prostate carcinomas, and blood from patients with metastatic prostate cancer. PTI-1 consists of a unique 5 untranslated region (5 UTR) with significant sequence homology to Mycoplasma hyopneumoniae 23S ribosomal RNA juxtaposed to a sequence that encodes a truncated and mutated human elongation factor 1␣ (Trun-EF). Stable expression of a nearly full-length 1.9-kb PTI-1 gene, but not the separate PTI-1 5 UTR or Trun-EF region, in normal rat embryo fibroblast cells, CREF-Trans 6, induces an aggressive tumorigenic phenotype in athymic nude mice. Blocking PTI-1 expression with antisense PTI-1 results in reversion of transformed PTI-1-expressing cells to a more normal cellular morphology with suppression in both anchorage-independent growth and tumorigenic potential in athymic nude mice. These findings document that PTI-1 is indeed an oncogene, and directly blocking PTI-1 expression can nullify cancer phenotypes. In these contexts, PTI-1 not only represents a gene with discriminating diagnostic properties but also may serve as a target for the gene-based therapy of human prostate and other cancers.Prostate cancer is the most frequently diagnosed internal cancer of men in the United States and the second leading reason for cancer-related deaths of men (1-3). These statistics underscore the need for improved molecular staging of and therapeutic approaches for this prevalent neoplastic disease.