In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast.

We have studied the expression of the c-myc protooncogene and the cycle-dependent histone 4 gene at the cellular level by RNA:RNA in situ hybridization in 18 primary breast ductal adenocarcinomas. These tumors have previously been examined by Southern and Northern blot analysis for the genomic status of c-myc and its expression, respectively (Escot et al., Proc. Natl. Acad. Sci. USA, 83: 4834-4838, 1986). Positive c-myc hybridization signals were associated with carcinoma cells in all cases, including tumors which had no apparent alterations of the c-myc locus. Steady-state levels of c-myc mRNA appeared heterogeneous in carcinomas with similar histology. High levels of hybridization were found in four of seven tumors with strong amplification of the c-myc locus. Similarly high levels of c-myc hybridization were detected in two of nine cases which had an apparently normal c-myc locus but comparatively low cellularity. In addition to carcinoma cells, dense clusters of infiltrating lymphocytes, present in three tumors, exhibited c-myc hybridization. The expression of the histone 4 gene failed to correlate with levels of c-myc expression. We conclude that in infiltrating ductal carcinomas: (a) the c-myc protooncogene is transcriptionally activated; (b) c-myc amplification is probably underestimated due to heterogeneous cellularity; (c) high-level c-myc amplification is related to high-level expression, but other unknown factors also may play a role; (d) differences in levels of c-myc expression may not only be attributed to differences in the growth fractions; and (e) c-myc mRNA in total RNA from biopsy samples may be contributed by infiltrating lymphocytes.

[1]  J. Varley,et al.  Differential expression of cellular oncogenes in benign and malignant human breast tissue , 1986, International journal of cancer.

[2]  P. Nowell,et al.  Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. , 1986, Science.

[3]  J. Rowley,et al.  Gene encoding the alpha chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8;14 translocation in a cell line from a human T-cell leukemia. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Pelicci,et al.  Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Gallo,et al.  Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Yokota,et al.  Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. , 1986, Science.

[7]  L. Kaczmarek,et al.  Expression of c-myc and other cell cycle-dependent genes in human colon neoplasia. , 1985, Cancer research.

[8]  C. Betsholtz,et al.  Cell-type-specific pattern of myc protooncogene expression in developing human embryos. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Erisman,et al.  Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene , 1985, Molecular and cellular biology.

[10]  C. Heldin,et al.  Coexpression of the sis and myc proto-oncogenes in developing human placenta suggests autocrine control of trophoblast growth , 1985, Cell.

[11]  R. Eisenman,et al.  c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells , 1985, Nature.

[12]  P. Leder,et al.  Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes , 1984, Cell.

[13]  D. Melton,et al.  Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. , 1984, Nucleic acids research.

[14]  R. Ohlsson,et al.  Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: Implications for embryonic cell proliferation , 1984, Cell.

[15]  G. Stein,et al.  Expression of histone genes in a G1-specific temperature-sensitive mutant of the cell cycle. , 1984, Biochemistry.

[16]  M. Cole,et al.  Transcriptional activation of the translocated c-myc oncogene in mouse plasmacytomas: Similar RNA levels in tumor and proliferating normal cells , 1984, Cell.

[17]  I. Verma,et al.  Expression of cellular oncogenes in human malignancies. , 1984, Science.

[18]  D. Kozbor,et al.  Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. , 1984, Cancer research.

[19]  R. Angerer,et al.  Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. , 1984, Developmental biology.

[20]  H. E. Gray,et al.  Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation , 1984, Cell.

[21]  P. Leder,et al.  Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor , 1983, Cell.

[22]  Stanley J. Watson,et al.  Identification of proopiomelanocortin neurones in rat hypothalamus by in situ cDNA-mRNA hybridization , 1983, Nature.

[23]  E. Kandel,et al.  In situ hybridization to study the origin and fate of identified neurons. , 1983, Science.

[24]  P. Leder,et al.  Translocations among antibody genes in human cancer. , 1983, Science.

[25]  J. Minna,et al.  Amplification and expression of the c-myc oncogene in human lung cancer cell lines , 1983, Nature.

[26]  J Erikson,et al.  Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. , 1983, Science.

[27]  G. Stein,et al.  Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. , 1983, Nucleic acids research.

[28]  H. Varmus,et al.  Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Leder,et al.  Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Gallo,et al.  onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient , 1982, Nature.

[31]  M. Groudine,et al.  Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line , 1982, Nature.

[32]  G. Stein,et al.  Organization of human histone genes. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. M. Tener,et al.  Acetylation of chromosome squashes of Drosophila melanogaster decreases the background in autoradiographs from hybridization with [125I]-labeled RNA. , 1978, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[34]  F. Amaldi,et al.  Autoradiographic Detection of Molecular Hybrids between rRNA and DNA in Tissue Sections , 1970, Nature.

[35]  M. Birnstiel,et al.  RNA-DNA Hybrids at the Cytological Level , 1969, Nature.

[36]  J. Gall,et al.  Formation and detection of RNA-DNA hybrid molecules in cytological preparations. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[37]  F. Alt,et al.  Differential expression of myc family genes during murine development , 1986, Nature.

[38]  M. Groudine,et al.  Levels of c-myc oncogene mRNA are invariant throughout the cell cycle , 1985, Nature.

[39]  H. Varmus.  The molecular genetics of cellular oncogenes. , 1984, Annual review of genetics.

[40]  P. Leder,et al.  The regulation of c-myc by growth signals. , 1984, Current topics in microbiology and immunology.