Grants and Contracts Details
Human breast cancer is an enormous world-wide problem. We have obtained preliminary data showing that some of the worst types of human breast cancers contain a small protein called CD151. Furthermore, we have discovered that CD151 protein is not simply present, but also is contributing to breast cancer having a bad outcome. To make this discovery, we used a mouse, genetically engineered to undergo spontaneous breast cancer formation. When the CD151 gene was removed from that mouse, spontaneous formation of breast cancer was considerably delayed. In another experiment, removal of CD151 from human breast cancer cells caused them to grow more slowly when implanted into a mouse. These preliminary findings strongly suggest that CD151 protein contributes to the progression of multiple subtypes of breast cancer. Additional preliminary experiments were aimed at discovering what CD151 is doing in breast cancer cells. When we removed CD151 from these cells, several things happened. First, the cells were no longer able to respond to growth factors – small soluble proteins that stimulate tumor growth and movement. Second, the breast tumor cells no longer were able to invade into artificial membranes. Third, the breast cancer cells lost their ability to transmit key molecular signals to the inside of the cell. Fourth, several important proteins that are normally clustered on the surface of breast tumor cells became disorganized and disconnected. These preliminary results give good initial insights into how CD151 functions on mammary tumor cells. Though suggestive, our preliminary results are not definitive. Now we seek to establish whether the presence of CD151, in a statistically significant manner, correlates with loss of survival in humans with breast cancer. Also, we will determine whether the absence of CD151 protein causes multiple types of breast cancer to be significantly delayed in mice. In addition, we will investigate whether interference with CD151 can make breast cancer cells more sensitive to drugs that inhibit growth factors. Finally, we will identify specific molecules and pathways that are organized by CD151 protein, while contributing to breast cancer growth and invasion. Our proposed experiments may lead to improved therapy for breast cancer. If we can show that CD151 is indeed contributing to breast cancer progression, then the next step would be to design drugs that inhibit CD151, thereby inhibiting breast cancer progression. Identification of key molecules that interact with CD151 should enable the intelligent design of anti-CD151 drugs that are specific and effective. If interfering with CD151 does indeed make breast cancer cells more sensitive to drugs that inhibit growth factors, that would represent a major step forward in improving the effectiveness of those drugs, which are increasingly being utilized clinically. Finally, because CD151 is not needed for normal life, it may be possible to design drugs that inhibit CD151 without causing too many unwanted side effects.
|Effective start/end date||4/19/10 → 4/18/11|
- Susan G Komen Breast Cancer Foundation: $186,837.00
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