Expression of Human Endogenous Retrovirus Type K
Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer
I recently happened to read an interesting short
report published in August 2011 issue of Genes and Cancer.
In this study, the authors evaluated the use of expression of envelope (env)
protein of human endogenous retroviruses-K (HERV-K) as a prognostic marker of
breast cancer. HERVs constitute about 8% of human genome. There are many
distinct families of HERVs present in human genome. Most of these families are
defective and could not encode complete viruses. However, HERV-K family shows a
conservation of seemingly intact retroviral genes as it is one of the most
recently integrated viruses. In a previously conducted study, the
authors observed the expression of HERV-K env mRNA and protein in breast cancer
tissues obtained from US women. To further study the role of HERV-K env mRNA as
a prognostic marker for breast cancer, the authors looked at expression of
HERV-K env mRNA and protein in breast cancer tissues obtained from both Chinese
and US women. The authors also analyzed the relationship between HERV-K env
expression and disease severity in these women.
Methodology and Results:
One hundred and twenty tissues from Chinese
women including 40 breast cancer tissues, 40 matched adjacent uninvolved breast
tissues and 40 breast tissues from benign breast diseases but not cancer were
used in this study. HERV-K env mRNA was detected in 70% of breast cancer
samples and 20% of surrounding uninvolved tissues from breast cancer patients.
No HERV-K env mRNA was detected in breast tissues from control patients.
Similar to mRNA results, HERV-K env protein expression was also higher in
cancer tissues in comparison to controls. The authors also found medium to
strong expression of env protein in cancerous tissues and weak to no expression
in adjacent non-cancerous tissues.
The authors then looked at relationship between
expression level of HERV-K protein and clinical features of the patients. 82%
of the patients with high expression of HERV-K in their tumor had a tumor size
greater than 3 cm. HERV-K env expression also correlated with other clinical
and pathological characteristics in these patients. Furthermore, the scientists
conducted a Kaplan-Meier survival analysis and found that the patients with
high expression of HERV-K env protein had a significantly shorter overall
survival in comparison with patients with moderate to low HERV-K env protein expression.
Taken together, all these results indicate that
HERV-K env protein expression is highly upregulated in human breast cancer
tissues and not in adjacent non-cancerous tissues or normal breast tissues.
In all the paper is nicely written and all the
experiments seems to be nicely conducted. However, this paper exclusively talks
about env but what about pol and gag? Expression of pol is particularly
important as pol encodes for reverse transcriptase, which is required for
production of new virus progenies.
The study did not observe any association
between HERV-K env expression and ER/PR status. These results were surprising
as earlier studies have observed that expression of HERV-K mRNA and protein was
higher in breast cancer cell lines treated with estradiol and progesterone than
in cells without treatment
