Genetic changes could indicate an increase in tumour aggressiveness

OAS1 gene may be involved in the onset and progression of breast and prostate cancer, according to a recent study.

A team of researchers from Portugal have discovered that genetic changes in the gene oligodenylate synthetase 1 (OAS1) could be associated with the aggressiveness of tumors in breast and prostate cancer.

Their research paper, published in the latest issue of the gold open-access peer-reviewed journal of Advances in Modern Oncology Research, showed that the OAS1 gene was under-expressed in both breast and prostate cancer.

According to the researchers, OAS1 catalyses the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A), which then binds and activates Ribonuclease L (RNase L). In its activated form, RNase L cleaves all RNA molecules in the cell, thus leading to cell death.

The suppression of RNase L activity in cancer cell lines dramatically blocked cell death, according the researchers. "Furthermore, the OAS/RNase L pathway has been associated with the inhibition of cell growth and promotion of apoptosis in human breast and prostate cancer cell lines," they explained.

In addition, OAS1 also plays an inherent role in controlling cell growth and differentiation. Lower levels of OAS1 in breast and prostate cancer cases indicate that the OAS1/RNase L apoptotic pathway may be compromised in breast and prostate tumours.

Using immuno-histochemistry (IHC), the team analyzed and compared OAS1 protein in samples of infiltrating ductal carcinoma (IDC) and normal breast cancer, as well as samples of adenocarcinoma of prostate, benign prostatic hyperplasia (BPH) and normal prostate cancers.

"[W]e hypothesized that OAS1 gene was found to be differentially expressed in human breast and prostate cancer specimens. In order to attain this goal, the mRNA expression of OAS1 was determined in matched tumour-normal adjacent tissue pairs," stated the researchers led by Cláudio Jorge Maia, Assistant Professor at Faculty of Health Sciences of University of Beira Interior (UBI).

"Our results showed that OAS1 gene was under-expressed in IDC of breast specimens when compared to normal adjacent tissue," the researchers stated.

"It should be noticed that a negative correlation was found between OAS1 protein expression and tumour grading, suggesting that OAS1 expression decreased in aggressive tumours," the team reported.

They continued, "The OAS1 protein levels in samples of adenocarcinoma of prostate and benign prostate hyperplasia were also investigated by IHC. The results suggested that OAS1 protein expression was lower in malignant lesions."

Taking into account that OAS1 levels were lower in both breast and prostate cancers than in normal tissue, "the aggressiveness of the tumours correlated positively with lower levels of OAS1 expression, and considering the role of OAS1 in apoptosis, it is liable to speculate that apoptosis induced by the OAS/RNase L pathway may be compromised in these cancers," explained the researchers in their paper.

Maia and his team also evaluated OAS1 levels in response to the sex steroid hormones, oestrogens and androgens, in breast and prostate cancer cell lines. They used 17β-estradiol (E2) and dihydrotesterone (DHT) and analyzed the effects on both cancer cell lines, respectively.

"The OAS/RNase L system is associated with the inhibition of cell growth and promotion of apoptosis. Our results suggested that E2 may enhance the reduction of OAS1 expression in breast tumours, which may further compromise the OAS/RNase L apoptotic pathway," the team explained.

"However, the results obtained with the DHT showed no effect in the regulation of OAS1 expression in human prostate cancer cell lines," they continued.

On the whole, the results that were elucidated from this study supported the hypothesis that genetic changes in OAS1 gene could be involved in the progression of breast and prostate cancer, although the researchers stressed that further investigation is needed as a putative target for cancer management.

It is also observed that OAS1 expression was down-regulated by E2 in human breast cancer cell lines but DHT has no effect in the regulation of OAS1 expression in human prostate cancer cell lines.