Growth Factors in Human Germ Cell Cancer

  • W. H. MillerJr.
  • E. Dmitrovsky
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 123)


A growing body of evidence suggests that malignancy often represents a failure of differentiation. Several model systems have been developed that show an inverse relationship between differentiation and malignancy. As tumor cells differentiate, they typically lose proliferative potential and the ability to cause tumors when implanted into susceptible hosts. Thus, an understanding of the cellular mechanisms of differentiation may yield insight into the mechanisms of the abnormal regulation of growth by cancer cells. Murine and human models of differentiation of tumor cells, including mouse erythroleukemia (MEL) cells, human leukemic cell lines, and mouse F9 teratocarcinoma cells, have been used to explore changes in the expression of important growth-regulated genes, such as cellular oncogenes and growth factors, as a function of differentiation induced in vitro. For example, a biphasic decline of c-myc and c-myb mRNA levels has been seen following dimethyl sulfoxide (DMSO) induction of MEL cells (Ramsey et al. 1986). Indeed, some authors have suggested a causal relationship between the downregulation of oncogene products and both differentiation and loss of malignancy. This has been supported by experiments showing that expression of transfected c-myc or c-myb genes into MEL cells blocks the induction of differentiation by DMSO (Dmitrovsky et al. 1986; Clarke et al. 1988). Differentiation of F9 cells can be induced by retinoic acid (RA) and dibutyryl cAMP and, as in MEL cells, is accompanied by specific changes in expression of protooncogenes, biochemical markers, developmentally active genes, and growth factors (reviewed in Miller et al. 1990a). These changes correlate with a decline in the malignant and proliferative potential of these differentiated cells (Strickland and Sawey 1980; Strickland and Mahdavi 1978).


Retinoic Acid Retinoic Acid Treatment Teratocarcinoma Cell Germ Cell Cancer Human Germ Cell 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • W. H. MillerJr.
    • 1
  • E. Dmitrovsky
    • 1
  1. 1.Laboratory of Molecular Medicine, Department of MedicineMemorial Sloan-Kettering Cancer Center, Cornell University Medical CollegeNew YorkUSA

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