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Histochemical expressing genes as ultrasensitive markers for micrometastasis studies

Lin, Wen-chang
http://rave.ohiolink.edu/etdc/view?acc_num=case1059657986

Abstract Details

1992, Doctor of Philosophy, Case Western Reserve University, Molecular Biology and Microbiology.
Evaluation of micrometastasis formation at secondary organs has been an important issue in cancer treatment, as well as in understanding metastasis mechanisms. A model system, with bacterial β-galactosidase (lacZ) gene as an ultrasensitive histochemical marker for identifying transfected metastatic tumor cells, was developed to overcome the inability of identifying single metastatic tumor cells in situ. With a chromogenic substrate (X-gal), the lacZ-bearing EJ Ha-ras oncogene-transformed tumor cells stain intensely blue and can be easily distinguished from the host tissue cells at minutes to weeks post-injection. The lacZ marker gene appears to be an ultrasensitive marker for analyzing the earliest stages in micrometastasis development. In order to study interactions of different tumor cell clones, as well as between tumor cells and host cells, alternative histochemical marker genes (human placental alkaline phosphatase and Drosophila alcohol dehydrogenase) were developed for multiple-color marker tagging systems. Cells carrying different marker genes can easily be differentiated with double-staining protocols. Co-injection or sequential-injection experiments with two classes of transformed cells carrying different oncogenes (ras or sis) and alternative histochemical markers (β-galactosidase or alkaline phosphatase) demonstrate cooperation among different oncogene-transformed cells. The ultrasensitivity of these histochemical markers provides opportunities to evaluate quantitatively the metastatic potential of different tumor cell lines, examine the genetic instability as well as clonal dominance/evolution of metastatic cells, follow the development of micrometastasis at multiple organs in situ, and study expression of growth-related genes in micrometastatic foci at the single-cell level. Therefore, these marker genes allow us to analyze qualitatively and quantitatively not only the development of micrometastases at their earliest stages, but also their interaction with host cells and clonal progression within metastatic tumor cells
Lloyd Culp (Advisor)
258 p.
Biology, Molecular
Histochemical marker genes; Micrometastasis

Recommended Citations

Citations

  • Lin, W.-C. (1992). Histochemical expressing genes as ultrasensitive markers for micrometastasis studies [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1059657986

    APA Style (7th edition)

  • Lin, Wen-chang. Histochemical expressing genes as ultrasensitive markers for micrometastasis studies. 1992. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1059657986.

    MLA Style (8th edition)

  • Lin, Wen-chang. "Histochemical expressing genes as ultrasensitive markers for micrometastasis studies." Doctoral dissertation, Case Western Reserve University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=case1059657986

    Chicago Manual of Style (17th edition)

case1059657986
325
© 1992, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.