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R G Lopez

Publications and source records attributed to R G Lopez.

6 recordsLinked to original sources
PubMed2006

Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation.

The transcription factor hypoxia inducible factor 1 (HIF1), an HIF1alpha-aryl hydrocarbon receptor nuclear translocator (ARNT) dimeric factor, is essential to the cellular response to hypoxia. We described a t(1;12)(q21;p13) chromosomal translocation in human acute myeloblastic leukemia that involves the translocated Ets leukemia (TEL/ETV6) and the ARNT genes and results in the expression of a TEL-ARNT fusion protein. Functional studies show that TEL-ARNT interacts with HIF1alpha and the complex binds to consensus hypoxia response element. In low oxygen tension conditions, the HIF1alpha/TEL-ARNT complex does not activate transcription but exerts a dominant-negative effect on normal HIF1 activity. Differentiation of normal human CD34+ progenitors cells along all the erythrocytic, megakaryocytic and granulocytic pathways was accelerated in low versus high oxygen tension conditions. Murine 32Dcl3 myeloid cells also show accelerated granulocytic differentiation in low oxygen tension in response to granulocyte colony-stimulating factor. Interestingly, stable expression of the TEL-ARNT in 32Dcl3 subclones resulted in impaired HIF1-mediated transcriptional response and inhibition of differentiation enhancement in hypoxic conditions. Taken together, our results underscore the role of oxygen tension in the modulation of normal hematopoietic differentiation, whose targeting can participate in human malignancies.

Animals↗
PubMed2000

Characterization of a novel ETS gene, TELB, encoding a protein structurally and functionally related to TEL.

The TEL/ETV6 gene is located at 12p13 and is frequently involved in chromosomal translocations in human malignancies usually resulting in the expression of fusion proteins between the amino terminal part of TEL, and either unrelated transcription factors or protein tyrosine kinases. We report here a novel gene named TELB which is located on human chromosomal band 6p21 and encodes a protein highly related to TEL. TELB is widely expressed in different tissues and, similarly to TEL encodes a sequence-specific transcriptional repressor.

Amino Acid Sequence↗
PubMed1999

TEL is a sequence-specific transcriptional repressor.

TEL is a gene frequently involved in specific chromosomal translocations in human leukemia and sarcoma that encodes a member of the ETS family of transcriptional regulators. TEL is unusual among other ETS proteins by its ability to self-associate in vivo, a property that is essential to the oncogenic activation of TEL-derived fusion proteins. We show here that TEL is a sequence-specific transcriptional repressor of ETS-binding site-driven transcription of model and natural promoters. Deletion of the oligomerization domain of TEL or its substitution by the homologous region of monomeric ETS1 impaired the ability of TEL to repress. In contrast, substitution of the oligomerization domain of TEL by unrelated oligomerization domains resulted in an active repressor, showing that the ability of TEL to repress depends on its ability to self-associate. The study of the properties of TEL fusions to the heterologous DNA binding domain of Gal4 identified two autonomous repression domains in TEL, distinct from its oligomerization domain, that are essential to the ability of TEL to repress ETS-binding site-containing promoters. These results have implications for the normal function of TEL, its relation to other ETS proteins, and its role in leukemogenesis.

Animals↗
PubMed1977

The value of pre-therapy peritoneoscopy in localized ovarian cancer.

Because of the recent reports indicating the high incidence of unsuspected diaphragmatic metastases in presumed localized ovarian cancer, we have carried out peritoneoscopy on 14 consecutive patients referred with the diagnosis of Stage I or II ovarian cancer. Of the 14 women none was demonstrated to have diaphragmatic metastases, but 35 per cent were found to have cytologic washings demonstrating malignant cells. The significance of these findings is discussed.

Cytodiagnosis↗
PubMed1975

Paget's disease of the vulva: a clinicopathologic study of eight cases.

Clinicopatholigic findings in 8 patients with Paget's disease of the vulva are presented with a discussion if its pathogenesis. In 7 cases the disease was intraepithelial, and in 1 it was accompanied by underlying adenocarcinoma. The treatment of choice is surgical. The importance of early diagnosis, adequate excision, and close followup is emphasized. In 2 cases, the disease was associated with carcinoma of the breast and in 1 case with carcinoma of the liver.

Adenocarcinoma↗