New! Sign up for our free email newsletter.
Science News
from research organizations

Breast cancer gene a potential target for childhood liver cancer treatment

September 3, 2019
Osaka University
Hepatoblastoma is a rare liver cancer that mainly affects infants and young children. Researchers confirmed that breast cancer gene GREB1 plays a major role in hepatoblastoma cell proliferation. By interfering with GREB1 protein production, tumor formation was inhibited in a mouse liver cancer model, suggesting this approach could be used to develop a targeted hepatoblastoma therapy.

Hepatoblastoma is a rare form of liver cancer affecting just a few individuals per million. However, it is the leading cause of liver cancer in infants and young children, with most patients diagnosed before their third birthday.

While advances in surgery and chemotherapy have meant that the prognosis for hepatoblastoma patients is generally quite good, aggressive forms of the disease leave some young patients with few treatment options and poor long-term survival rates. In a study published at 18:00 (JST) on Aug. 28 in Nature Communications, researchers from Osaka University have built on prior research to make a breakthrough in our understanding of the causes of hepatoblastoma, identifying a gene that could be key to developing a targeted therapy.

As far back as 1999, researchers realized that a large number of hepatoblastoma patients -- up to 90% in some cases -- carry mutations in a gene called β-catenin. As part of the Wnt/β-catenin signaling pathway, the β-catenin protein activates genes needed for cellular growth and differentiation. If left unchecked, β-catenin accumulation can result in tumor formation. Mutations in Wnt/β-catenin signaling components often lead to β-catenin accumulation and are common in several forms of cancer.

"We decided to screen uncharacterized Wnt/β-catenin target genes in liver tumor cells to try and identify novel genes with a role in the development of hepatoblastoma," explains lead author of the study Shinji Matsumoto. "One of the most abundantly expressed genes was growth regulation by estrogen in breast cancer 1 (GREB1), which is a well-known estrogen-responsive gene implicated in the growth of breast cancer cells."

While well-characterized in breast cancer, no one had determined that GREB1 was actually a target of Wnt/β-catenin signaling, and its role in non-hormone-sensitive tumor development was unconfirmed.

But after studying the protein in more detail, it became obvious to the researchers that GREB1 could be a major player in the development of hepatoblastoma.

"Overexpression of β-catenin in a mouse liver cancer model resulted in tumor formation and an increase in GREB1 expression," says corresponding author Akira Kikuchi. "If we then suppressed the production of GREB1, we saw a decrease in hepatoblastoma cell proliferation and therefore fewer tumors in the study animals."

Because GREB1 is active in the nucleus, the researchers attempted to prevent tumor formation using amido-bridged nucleic acid-modified antisense oligonucleotides. These small single-stranded DNA molecules specifically interfere with the production of target proteins by binding to the mRNA. Significantly, the GREB1-targeted oligonucleotides successfully decreased GREB1 production and suppressed the formation of hepatoblastoma tumors.

Using this strategy, it is hoped that a GREB1-targeted therapy can now be developed to specifically treat hepatoblastoma.

Story Source:

Materials provided by Osaka University. Note: Content may be edited for style and length.

Journal Reference:

  1. Shinji Matsumoto, Taku Yamamichi, Koei Shinzawa, Yuuya Kasahara, Satoshi Nojima, Takahiro Kodama, Satoshi Obika, Tetsuo Takehara, Eiichi Morii, Hiroomi Okuyama, Akira Kikuchi. GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-11533-x

Cite This Page:

Osaka University. "Breast cancer gene a potential target for childhood liver cancer treatment." ScienceDaily. ScienceDaily, 3 September 2019. <>.
Osaka University. (2019, September 3). Breast cancer gene a potential target for childhood liver cancer treatment. ScienceDaily. Retrieved December 1, 2023 from
Osaka University. "Breast cancer gene a potential target for childhood liver cancer treatment." ScienceDaily. (accessed December 1, 2023).

Explore More
from ScienceDaily