Breast Cancer
Characterisation of Genes Associated
with Sporadic Breast Cancer
Breast cancer is the number one cause of
cancer death among Australian women and exists in both sporadic
and inherited forms, with inherited cases accounting for about
10% and sporadic or non-inherited forms accounting for the
remaining forms. Various factors are involved in the development
of sporadic breast cancer and although this type of cancer
is clearly not inherited, it still involves gene variations
and genetic susceptibility.
Our research is aimed at investigating genes
involved in the development of the common sporadic form of
breast cancer. We are using a DNA analysis approach to detect
genes that are implicated in predisposition to this common
disease. We have recently identified several hormone-related
genes that are associated with the development of breast cancer.
These genes belong to the nuclear receptor gene family and
are involved in the normal day to day functioning of cells
within the body. DNA sequence changes in any of these genes
could potentially disrupt normal cell functions and result
in excess cell growth and the eventual development of a tumour.
Our results have recently shown that DNA
sequence changes in the vitamin D receptor, estrogen receptor
and glucocorticoid receptor genes can lead to an increased
risk for the development of sporadic breast cancer. Glucocorticoids
play an essential role in the body, regulating cell growth;
estrogens are also involved in the growth and division of
cells in the body; and vitamin D has been shown to inhibit
the growth of breast cancer cells in tumours. We are currently
undertaking further work, with recent funding from the Wesley
Research Institute, to determine how variations within these
genes specifically affect breast cancer development. Consequently,
we are undertaking gene expression, DNA binding and mutation
studies. We are also investigating other nuclear receptor
genes to see if they also play a role in breast cancer development.
Joanne Curran
Breast
Cancer Invasiveness Research
Breast cancer remains the highest cause of
cancer deaths in the female Australian population. In the
US the prevalence follows closely behind cancers of the respiratory
tract and lungs. Despite the increasing research effort over
the last 20 years, the underlying biology of cancer development
and its effect on clinical pathology and patient survival
remains largely unknown. Breast cancer is a heterogeneous
disease, made up of over 18 different grades and classifications
that rely upon largely morphology and cytological classifications,
and the development of secondary metastases. Unlike prostate
cancer diagnosis, which relies upon prostate specific antigen
as a marker of tumor progression, there remains no consensus
objective diagnostic marker of breast cancer mortality.
One of the goals of the breast cancer research
group has been to identify the genes involved in breast cancer
progression or invasiveness. The work has been approached
in several ways by examining the effect of the loss of hormone
receptor expression on breast tissue and also investigating
the role matrix metalloproteases play on tumour development.
These genes are believed to be vital factors involved in metastasis.
However, which specific genes and how they act in invasion
and in which particular types or grades of tumour, has not
yet been determined This work uses breast cancer cell lines
maintained to confirm results obtained from human breast cancer
tissue. The work has also been involved in developing techniques
that allow us to examine gene expression in archival biopsy
material from stored sample sources.
We believe that the work has amazing potential
to uncover the underlying biology of cancer development, answer
questions related to normal and abnormal tissue development
and to provide practical prognostic tools for clinical pathology
that will assist in more effective and early diagnosis. Finally
all this work has been backed up with basic work examining
gene structure, the effect of inherited (familial) and sporadic
mutations (single nucleotide polymorphisms, SNPs) on gene
expression and the link with cancer susceptibility.
Albert Mellick
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