Induction of Differential Growth in vitro by
High-risk Human Papillomavirus in Human Breast
Cancer Cell Lines is Associated with Caspase Dysregulation |
Karl Kingsley1*§, Jennifer Zuckerman2, Morghan Davis2, Matt Matteucci2, Aubrey Knavel2, Jacqueline Rinehart2, Van Tran2, Demian Woyciehowsky2, Phillip Jenkins2, Rui Yu3, Dieu-Hoa Nguyen3, Susan O’Malley1§ |
| 1Department of Biomedical Sciences, School of Dental Medicine, University of Nevada, Las Vegas |
| 2Department of Clinical Sciences, School of Dental Medicine, University of Nevada, Las Vegas |
| 3Department of Biological Sciences, University of Nevada, Las Vegas |
| §These authors contributed equally to this work |
| *Corresponding author: |
Dr. Karl Kingsley, Department of Biomedical Sciences,
School of Dental Medicine,
University of Nevada, Las Vegas,
E-mail : karl.kingsley@unlv.edu |
|
| Received October 28, 2009; Accepted November 30, 2009; Published
November 30, 2009 |
| Citation:Kingsley K, Zuckerman J, Davis M, Matteucci M, Knavel A, et al. (2009) Induction of Differential Growth in vitro by High-risk Human Papillomavirus in Human Breast Cancer Cell Lines is Associated with Caspase Dysregulation. J Cancer Sci Ther 1: 062-071. doi:10.4172/1948-5956.1000010 |
| Copyright: ©2009 Kingsley K, et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited. |
| Abstract |
Introduction |
| Many viruses have been associated with human breast
cancers, including Epstein-Barr and Cytomegalovirus.
New evidence has revealed the frequent presence of highrisk
human papillomavirus (HPV) strains HPV16 and
HPV18 in breast carcinoma biopsies. These findings raise
the question of whether HPV may infect developing cancers
and mediate their growth and development, as was
recently observed with oral cancers. The goal of this study
is to test the hypothesis that these high-risk HPV strains
are sufficient to significantly alter phenotypes of already
transformed human breast cancer cell lines. |
Materials and methods |
| A series of in vitro experiments, including proliferation,
adhesion and viability assays, were used to quantify the
effects of HPV16 and HPV18 on the human breast cancer
cell lines, T-47D and MCF7, following transient transfection
with the full length HPV virus. Normal breast and
fibroblast cell lines, MCF10A and Hs27, were used as noncancerous
controls. |
Results |
HPV16 and HPV18 significantly inhibited proliferation
and adhesion of T-47D cells, although viability was not
affected. Differential effects on proliferation were observed
in MCF7 cells; HPV16 inhibited proliferation,
while HPV18 stimulated proliferation. No measurable
effects in adhesion or viability in MCF7 cells were observed.
The phenotypic changes in T-47D and MCF7 cells
were associated with changes in mRNA expression of
caspase-2,-3 and -8, but not p53 or GAPDH. No measurable
changes in proliferation or viability were observed
following HPV transfection in the normal human breast
cell line, MCF10A, or the normal human fibroblast cell
line, Hs27, although adhesion was differentially affected. |
Conclusions |
Although HPV is a primary cause of virtually all cervical
cancers, it is found as a concomitant infection in many
other tumors. While HPV may initiate carcinogenesis in these tumors, recent studies suggest HPV may also modulate
the progression or malignancy process in already transformed
cancers. Determining what effects HPV has on
already transformed breast cancers may therefore become
an important step towards understanding the factors that
will lead to more effective treatment options for a significant
proportion of breast cancer patients.
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