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Suppressor genes in breast cancer: An overview

  • Patricia S. Steeg
Part of the Cancer Treatment and Research book series (CTAR, volume 61)

Abstract

Over the past 10 years a multitude of oncogenes have been discovered, and considerable progress has been made in the characterization of their biochemical functions/malfunctions [reviewed 1]. Cell-fusion studies have predicted the existence of suppressor genes for both the tumorigenic and metastatic components of cancer progression [2, 3, 4]. The general location of many putative suppressor genes was identified on the basis of chromosomal alterations, usually deletions, often in cancer types with a high risk of inheritance. One characteristic of many suppressor genes postulated to date is their homozygous inactivation in cancer cells, by deletion and/or mutation, consistent with Knudson’s hypothesis [5]. Additional data, including experiments described herein for breast cancer, suggest that structural and/or regulatory alterations to suppressor genes, in the absence of homozygous inactivation, may also impact the cancer phenotype. Transfection experiments, however, remain the only accepted confirmation of a suppressive function. In these experiments the suppressor gene is transfected with a marker gene (usually antibiotic resistance) into tumor cells, and changes to a more ‘normal’ phenotype are noted. These experiments are fraught with difficulties, making their interpretation difficult: Often, transfection of the suppressor gene construct generates significantly fewer antibiotic-resistant colonies than a side-by-side transfection with a control construct. For p53, many of the transfected colonies that grew had p53 mutations [6]. Although there are other possible interpretations, the data suggest that those tumor cells expressing the transfected suppressor gene and exhibiting a more ‘normal’ phenotype do not readily grow out as a colony. This may be due to direct effects on cell division or other changes in differentiation, contact inhibition, senescence, or viability. In no case can it be established that a transfected clone expressing the wild-type suppressor gene, and exhibiting a more ‘normal’ phenotype, did not concurrently require mutation at another chromosomal locus. The difficulty in obtaining stable transfected clonal cell lines expressing the wild-type suppressor gene dictates that transfection experiments be reported in only a few tumor cell types.

Keywords

Breast Cancer Suppressor Gene Human Breast Carcinoma Transfection Experiment Allelic Deletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1991

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  • Patricia S. Steeg

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