The tumorigenic potential of a cell can be suppressed when it is fused with a nontumorigenic cell. Our previous work implicated chromosome 11 of a normal human cell as carrying tumorigenicity suppressor information. We are now attempting to verify this and to regionally localize (map) this genetic information which presumably regulates the expression of other genes, such as oncogenes (c-onc), that control normal cell differentiation but which may be functioning abnormally in malignant cells. This could lead to identification of these regulatory gene products, which could have therapeutic implications. DNA probes for polymorphic chromosome segments are used as markers to identify the cell parental origin of the chromosome 11 in intraspecies human cell hybrids. (1) Ongoing studies confirm the implication of the chromosome 11 of nontumorigenic diploid cells as carrying suppressor loci. (2) They also indicate chromosome 1 carries such loci and acts in concert with chromosome 11 in effecting stable suppression in cell hybrids. Regional localization of such loci with hybrids that contain only segments of these chromosomes are in progress. Related to the foregoing is an attempt to determine if the level of transcription of a c-onc gene is important for the malignancy of lymphoma cells. Tumorigenic human lymphoma cells with a t(8;14) chromosome are fused with nontumorigenic human diploid cells, as well as with B lymphocytes, and the tumorigenicity of the hybrids is tested in immunodeficient nude mice. The level of c-myc mRNA of the parental lymphoma cells is compared with that of the tumorigenically suppressed hybrids and of their tumorigenic derivatives to determine if suppression is associated with decreased transcription of c-myc. These findings are then correlated with immunoglobulin (Ig) expression and the chromosome content of the cells to determine if c-myc transcription correlates with expression of Ig genes (located very near c-myc on the t[8;14] chromosome) and if Ig expression and c-myc transcription are affected by a specific chromosome of the nontumorigenic cell. (M)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA016720-11
Application #
3164484
Study Section
(SSS)
Project Start
1979-09-01
Project End
1986-11-30
Budget Start
1985-04-01
Budget End
1986-11-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Kaelbling, M; Eddy, R; Shows, T B et al. (1991) Localization of the human gene allowing infection by gibbon ape leukemia virus to human chromosome region 2q11-q14 and to the homologous region on mouse chromosome 2. J Virol 65:1743-7
Kaelbling, M; Zhang, Y D; Dasgupta, U B et al. (1991) Nonrandom chromosome changes in methylnitrosourea (MNU) induced mouse T-cell lymphomas. Ann Genet 34:270-8
O'Hara, B M; Klinger, H P; Curran, T et al. (1987) Levels of fos, ets2, and myb proto-oncogene RNAs correlate with segregation of chromosome 11 of normal cells and with suppression of tumorigenicity in human cell hybrids. Mol Cell Biol 7:2941-6
Jhanwar, S C; Jensen, J T; Kaelbling, M et al. (1986) In situ localization of human fibronectin (FN) genes to chromosome regions 2p14----p16, 2q34----q36, and 11q12.1----q13.5 in germ line cells, but to chromosome 2 sites only in somatic cells. Cytogenet Cell Genet 41:47-53
O'Hara, B; Klinger, H P; Blair, D G (1986) Many oncogenes are transcribed in the D98AH2 derivative of the HeLa carcinoma cell line. Cytogenet Cell Genet 43:97-102
Kaelbling, M; Klinger, H P (1986) Suppression of tumorigenicity in somatic cell hybrids. III. Cosegregation of human chromosome 11 of a normal cell and suppression of tumorigenicity in intraspecies hybrids of normal diploid x malignant cells. Cytogenet Cell Genet 41:65-70
Kaelbling, M; Roginski, R S; Klinger, H P (1986) DNA polymorphisms indicate loss of heterozygosity for chromosome 11 of D98AH2 cells. Cytogenet Cell Genet 41:240-4
Klinger, H P; Kaelbling, M (1986) Suppression of tumorigenicity in somatic cell hybrids. IV. Chromosomes of normal human cells associated with suppression of tumorigenicity in hybrids with D98AH2 carcinoma cells. Cytogenet Cell Genet 42:225-35