Related Experiment Video
Updated: Jul 13, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis
1Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec, Canada. stephane.richard@mcgill.ca
Abstract:
The Src-associated substrate in mitosis Sam68 is a KH type RNA-binding protein known to be a substrate of numerous tyrosine kinases, and often referred to as a STAR (signal transduction activator of RNA) protein. Herein, we observed that Sam68-null mice display mammary gland and the uterine development defects. Moreover, we report that Sam68 haploinsufficiency impedes mammary tumor onset in vivo driven by the potent mammary-targeted polyoma middle T-antigen (MMTV-PyMT) oncogene. The effect was cell autonomous as the Sam68 knockdown in PyMT-transformed cell lines also delayed tumorigenesis and metastasis formation in nude mice. Interestingly, tumor extracts isolated from PyMT/Sam68(+/-) mice compared with PyMT/Sam68(+/+) mice contained activated Src and FAK kinases. These findings suggest that Sam68 may be a modulator of tyrosine kinase activity in vivo and a signaling requirement for mammary tumorigenesis and metastasis.
Insights
Sam68, a RNA-binding protein, is crucial for mammary gland development. Its absence or reduction impedes mammary tumor growth and metastasis by modulating tyrosine kinase activity.
Area of Science:
- Molecular Biology
- Oncology
- Developmental Biology
Background:
- Sam68 (Src-associated substrate in mitosis) is an RNA-binding protein and a substrate for tyrosine kinases.
- STAR proteins are involved in signal transduction and RNA regulation.
Purpose of the Study:
- To investigate the role of Sam68 in mammary gland development and tumorigenesis.
- To determine if Sam68 influences tyrosine kinase activity in vivo.
Main Methods:
- Analysis of Sam68-null mice for developmental defects.
- Mammary tumor induction using the MMTV-PyMT oncogene in Sam68 haploinsufficient mice.
- Sam68 knockdown in PyMT-transformed cell lines and subsequent tumorigenesis/metastasis studies in nude mice.
- Biochemical analysis of tyrosine kinase activity (Src, FAK) in tumor extracts.
Main Results:
- Sam68-null mice exhibit mammary gland and uterine development defects.
- Sam68 haploinsufficiency significantly delayed mammary tumor onset and metastasis in MMTV-PyMT mice.
- Sam68 knockdown in PyMT cells also reduced tumorigenesis and metastasis.
- Tumor extracts from Sam68 haploinsufficient mice showed increased Src and FAK kinase activity.
Conclusions:
- Sam68 plays a critical role in normal mammary gland and uterine development.
- Sam68 is essential for mammary tumorigenesis and metastasis, potentially by modulating tyrosine kinase signaling.
- Targeting Sam68 could be a therapeutic strategy for breast cancer.
Related Concept Videos
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...