Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library.
The HSP70 family of heat-shock proteins constitutes the major proteins synthesized in response to elevated temperatures and other forms of stress. In eukaryotes members of the HSP70 family also include a protein similar if not identical to bovine brain uncoating ATPase and glucose-regulated proteins. An intriguing relation has been established between expression of heat-shock proteins and transformation in mammalian cells. Elevated levels of HSP70 are found in some transformed cell lines, and viral and cellular gene products that are capable of transforming cells in vitro can also stimulate transcription of HSP70 genes. To determine the organization of this complex multigene family in the human genome, we used complementary approaches: Southern analysis and protein gels of Chinese hamster-human somatic cell hybrids, and in situ hybridization to human chromosomes. We demonstrate that functional genes encoding HSP70 proteins map to human chromosomes 6, 14, 21, and at least one other chromosome.
A translocation between chromosomes 3 and 8, t(3;8)(p14.2;q24.13), has been reported in a family with hereditary renal cell carcinoma. Using somatic cell hybrids, we have isolated, separately, both derivative chromosomes. We find that the c-myc oncogene (8q24
Human genes homologous to the v-erbA oncogene of avian erythroblastosis virus have been mapped to at least two human chromosomes. Recently, the ERBA2 gene was shown to encode a thyroid hormone receptor and localized to chromosome 3 by using flow-sorted chromosomes. We now demonstrate that this gene is located at 3p22-)3p24.1, using both somatic cell hybrids and in situ hybridization studies. Since this localization is close to the distal border of the small cell lung cancer (SCLC) 3pl4-3p23 deletion, we undertook additional studies to examine the ERBA2 gene in SCLC. Using somatic cell hybrids constructed from the SCLC line NCI-H182 as well as matched patient tumor and control tissue samples, we found that ERBA2 is variably deleted. Therefore, ERBA2 defines at the molecular level the distal border of the SCLC deletion and further implies that the putative suppressor gene is located centromeric of this locus. We also determined that, at least in NCI-H182, the 3pl4 breakpoint is proximal to the constitutive 3pl4.2 fragile site. These studies would indicate that the mechanism or initiation site of chromosomal rearrangement in SCLC is different from that which occurs during induction of the 3pl4 fragile site by aphidicolin. hybrids and in situ hybridization studies. This result suggested that ERBA2 might be useful in the analysis of the SCLC 3pl4-*3p23 deletion. Using SCLC cell lines and direct patient material and isolating a derivative chromosome 3 [der(3)] previously reported to contain a 3p14--3p23 deletion, we conclude that ERBA2 is variably deleted in SCLC samples. At the molecular level, this defines a region that must be telomeric to the critical segment containing a putative suppressor gene. The identification of an Msp I polymorphism should also facilitate genetic linkage studies to this region.The isolation of the der(3) chromosome from cell line NCI-H182 also provided a means to examine the proximal extent of the deletion. We found that the breakpoint is proximal to the common 3pl4.2 fragile site induced by aphidicolin. The fragile site appears to be closely related to the breakpoint in the hereditary renal cell carcinoma 3;8 translocation, t(3;8)(pl4.2;q24.1). Therefore, it would appear that a different initiation site of chromosomal rearrangement is involved in the generation of at least some 3p deletions in SCLC.
Rodent-human somatic cell hybrids containing single human chromosomes or chromosome fragments are extremely valuable in physical mapping, marker analysis, and disease mapping. Chromosome 21 has been extensively studied in this fashion, and a single set of hybrids has been utilized in mapping the majority of chromosome 21 markers. The utility of a set of hybrids depends upon the definition of the human chromosome content. Recently, Chumakov and coworkers (1) utilized 198 chromosome 21 markers in the preliminary analysis of YACs spanning chromosome 21q. We have used these same markers to evaluate the STS content of a set of 27 chromosome 21 somatic cell hybrids, resulting in the description of the breakpoints at the molecular level, as well as the definition of 35 "bins. " The detailed molecular definition of chromosome 21 content of the hybrids, in combination with the further analysis of chromosome 21 YACs (2), has resulted in the most detailed picture of chromosome 21 to date.
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