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Updated: Mar 8, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model
1State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
Abstract:
Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial-mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.
Insights
Star-PAP, a poly(A) polymerase, suppresses breast cancer growth by inducing apoptosis and sensitizing cells to chemotherapy. Its decreased expression correlates with poor prognosis, highlighting its tumor-suppressive role.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Star-PAP (poly(A) polymerase) is crucial for specific mRNA expression.
- The role of Star-PAP in cancer pathogenesis is largely unexplored.
- This study investigates Star-PAP's function in breast cancer.
Purpose of the Study:
- To determine the expression levels and pathological role of Star-PAP in breast cancer.
- To elucidate the molecular mechanisms underlying Star-PAP's function in cancer.
- To evaluate Star-PAP as a potential therapeutic target for breast cancer.
Main Methods:
- Analysis of Star-PAP expression in breast cancer cell lines and patient tissues.
- In vitro and in vivo experiments assessing the effects of Star-PAP overexpression and knockdown on cancer cell behavior.
- Investigation of Star-PAP's impact on apoptosis, proliferation, and response to chemotherapy.
- Evaluation of Star-PAP's role in epithelial-mesenchymal transition (EMT).
Main Results:
- Star-PAP expression was reduced in breast cancer tissues and cell lines.
- Overexpression of Star-PAP inhibited breast cancer cell proliferation and colony formation.
- High Star-PAP levels in patients correlated with improved prognosis.
- Star-PAP induced apoptosis via the mitochondrial pathway by regulating BIK expression.
- Star-PAP overexpression inhibited tumor xenograft growth and sensitized cells to chemotherapy.
- Star-PAP knockdown promoted mammary epithelial cell transformation and EMT.
Conclusions:
- Star-PAP exhibits significant tumor-suppressive activity in breast cancer.
- Star-PAP acts as a regulator of apoptosis and chemo-sensitivity.
- Star-PAP is a promising therapeutic target for novel breast cancer treatment strategies.
