Journal Article

Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells

Debasish Roy, Gloria Calaf and Tom K. Hei

in Carcinogenesis

Volume 22, issue 10, pages 1685-1692
Published in print October 2001 | ISSN: 0143-3334
Published online October 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.10.1685
Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells

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  • Clinical Cytogenetics and Molecular Genetics

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The development of human breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the transformation of normal human breast epithelial cells into neoplastic ones. Using a spontaneously-immortalized human breast epithelial (MCF-10F) cell line, we have shown previously that radiation, in combination with estrogen, induces a stepwise neoplastic transformation of this cell line. In the present study, we investigate the incidence of microsatellite instability and loss of heterozygosity using a battery of markers on chromosomes 6 and 17, we correlate the genetic alteration with the malignant transformation of the MCF-10F cell line ranging from altered morphology to increase in proliferative rate, anchorage independent growth and tumorigenicity in nude mice. Microsatellite markers were selected from the hot spot regions (6q21-q27, 17p12-p13.3 and 17q12-q21) of both chromosomes. We found that the frequency of allelic imbalance occurs at the different stages of tumor progression with a range of 21 to 50% depending on the marker studied. The relatively high rate of allele imbalance at all these loci suggests the presence and inactivation of one or more tumor suppressor genes in these regions. Thus, the present data will be useful for systematic studies to identify the cellular and molecular changes associated with radiation-induced breast carcinogenesis.

Keywords: DMEM, Dulbecco's modified Eagle medium; LOH, loss of heterozygosity; MSI, microsatellite instability; OD, optical density; PCR–SSCP, polymerase chain reaction–single strand conformation polymorphism; RER, replication error repair.

Journal Article.  5832 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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