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Biomedical subjects

H Roelink

Publications and source records attributed to H Roelink.

26 records · Page 2Linked to original sources
PubMed1993

Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene.

In mouse mammary tumors, the Wnt-3 gene can be activated by proviral insertion. Here we report on the isolation of a human homolog, WNT3. A genomic clone was isolated by use of mouse Wnt-3 sequences as a probe, after which cDNA containing most of the protein-encoding domain of the human gene was obtained by PCR. Comparison between the deduced mouse and human WNT-3 protein sequences showed four changes in 333 amino acids. WNT3 is located on chromosome 17q21. The gene was not found to be amplified or rearranged in a collection of human breast tumors.

Amino Acid Sequence↗
PubMed1992

Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors.

Mammary tumors in the GR strain are caused by a dominant locus containing an endogenous mouse mammary tumor provirus. Expression of this locus results in high virus titers, inducing tumors that progress from a hormone-dependent to a hormone-independent tumor state. We previously studied the activation of the Wnt-1 and int-2 oncogenes in several series of transplanted GR tumors and found that hormone-dependent early passages are generally oligoclonal for proviral integration at these genes. We have now re-examined several such tumor series for activation of other Wnt genes. In one series, the transition to hormone-independent growth was marked by the loss of the oligoclonal genotype and outgrowth of a hormone-independent cell population, clonal for the activation of Wnt-3. We show two examples of series of transplanted tumors that in later hormone-independent passages contain an amplified and overexpressed Wnt-2 gene, a novel mode of activation of these genes.

Animals↗
PubMed1991

Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube.

The Wnt gene family encodes a group of cysteine-rich proteins implicated in intercellular signaling during several stages of vertebrate development. This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors. Here we describe the molecular cloning of an additional member of the Wnt family, called Wnt-3A, and the spatial and temporal expression pattern of this gene as well as that of its close relative Wnt-3. The putative amino acid sequences of both proteins are almost 90% identical, but in situ hybridization to mouse embryo sections showed highly restricted patterns of expression of Wnt-3 and Wnt-3A, largely in separate areas in the developing nervous system. In the spinal cord Wnt-3 was expressed at low levels in the alar laminae and in the ventral horns, whereas Wnt-3A expression was confined to the roof plate. In the developing brain Wnt-3 was expressed broadly across the dorsal portion of the neural tube with a rostral boundary of expression at the diencephalon. In contrast, Wnt-3A was expressed in a narrow region very close to the midline; expression extended into the bifurcating telencephalon, in a highly localized fashion. Both Wnt-3 and Wnt-3A were expressed in the ectoderm, and Wnt-3A was also expressed in the periumbilical mesenchyme. Characteristic expression patterns of these two closely related genes suggest that Wnt-3 and Wnt-3A play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube.

Amino Acid Sequence↗
PubMed1990

Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain.

We have isolated a common insertion site, Wnt-3, for proviruses of the mouse mammary tumor virus (MMTV). Of mammary tumors induced by the GR variant of MMTV, 5% contains a provirus at Wnt-3, which is located on mouse chromosome 11. The gene is transcribed into a 3.8-kilobase (kb) mRNA in tumors with nearby proviral insertions but not in tumors with proviruses at other loci or in most adult tissues. Normal expression of Wnt-3 is detected in mouse embryos (with a peak around day 12 of gestation) and at low levels in adult brain. The transcriptional unit of the Wnt-3 gene spans approximately 55 kb, with a first intron of 36 kb. The deduced amino acid sequence of the Wnt-3 protein is 47% identical to the int-1/Wnt-1 gene product.

Amino Acid Sequence↗
PubMed1989

Transient expression of the proto-oncogene int-1 during differentiation of P19 embryonal carcinoma cells.

In mouse embryos, the int-1 proto-oncogene is transiently expressed in areas of the developing neural system. Retinoic acid-treated P19 embryonal carcinoma cells have often been used as an in vitro model for the molecular basis of neural development. We shown here that int-1 is transiently expressed in differentiated P19 cells. The time course and retinoic acid dose dependence of int-1 expression suggest that the gene is specifically expressed during early neural differentiation. P19 cells may be a useful model to assist in the study, at the cellular level, of the role of int-1 in neural development.

Animals↗
PubMed1983

Sequence homologies within the 5' end region of the estrogen-controlled vitellogenin gene in Xenopus and chicken.

In oviparous vertebrates vitellogenin, the precursor of the major yolk proteins, is synthesized in the liver of mature females under the control of estrogen. We have established the organization and primary structure of the 5' end region of the Xenopus laevis vitellogenin A2 gene and of the major chicken vitellogenin gene. The first three homologous exons have exactly the same length in both species, namely 53, 21 and 152 nucleotides, and present an overall sequence homology of 60%. In both species, the 5'-non-coding region of the vitellogenin mRNA measures only 13 nucleotides, nine of which are conserved. In contrast, the corresponding introns of the Xenopus and the chicken vitellogenin gene show no significant sequence homology. Within the 500 nucleotides preceding the 5' end of the genes, at least six blocks with sequence homologies of greater than 70% were detected. It remains to be demonstrated which of these conserved sequences, if any, are involved in the hormone-regulated expression of the vitellogenin genes.

Amino Acid Sequence↗