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NMSU professor awarded $1.48 million to study key to cancer drug’s resistance

https://newscenter.nmsu.edu/Articles/view/13668/nmsu-professor-awarded-1-48-million-to-study-key-to-cancer-drug-s-resistance

While involved in other research at New Mexico State University, chemistry and biochemistry professor Kevin Houston, discovered a key to what causes resistance to this drug. His progress has resulted in a recent $1.48 million, 4-year grant from the National Institutes of Health to take his research to the next level.

Houston and his team were studying steroid hormone signaling through an estrogen receptor called G protein-coupled estrogen receptor. They happened to notice when they treated breast cancer cells with tamoxifen, it increased the level of a secreted protein called insulin-like growth factor binding protein 1.

“This was interesting to me, not because of what we were studying, but because what I knew about breast cancer and the role of insulin-like growth factor in breast cancer proliferation,” Houston said. “We started pursuing it, little by little, and it turns out that this G protein-coupled estrogen receptor is important for tamoxifen to be able to increase the level of this binding protein, which inhibits breast cancer cell proliferation.”

Houston was working with Jeffrey Arterburn, NMSU Regents professor of chemistry and biochemistry, when he made his initial discovery. The New Mexico IDeA Networks of Biomedical Research Excellence and Cowboys for Cancer Research were the first to fund Houston’s research into tamoxifen resistance.

“The funding environment is extremely competitive, so this is really a great accomplishment,” Arterburn said. “It is also an example of how important seed grants and developmental funding are to enable young faculty to get their research projects going so that they have the publications and convincing data that will enable their grants to withstand the rigorous review process. The faculty in the chemistry and biochemistry department are all very happy and proud of Kevin for bringing in this important new grant, and wish him great success with this cancer research project.”

Some breast cancer patients do not respond to tamoxifen treatment at all and most patients will develop resistance. In his lab, Houston has developed tamoxifen resistant cells with binding protein, but the new grant will allow him to take his research much further.

“There are six binding proteins and we've only looked at one, and we want to understand how the other five binding proteins might be involved in tamoxifen treatment and resistance,” Houston said. “We also are going to study how binding protein 1 can change how classic estrogen receptors function. We have evidence we want to pursue as part of this grant showing how binding protein 1 changes estrogen’s ability to signal in the cells.

“Our third aim is to try to understand how the growth factor signaling pathways are involved in crosstalk. There are many receptors in cells. We have evidence that one of these receptors fundamentally changes in tamoxifen resistant cells.”

There are two other receptors Houston’s team has observed fundamentally change: EFGR and IGF-2 receptors. Through his research they want to discover how the three receptors work together in tamoxifen resistance.

The NIH grant will allow Houston to hire a postdoctoral fellow along with two or three graduate students. He also invites four or five undergraduate students to participate in his lab. Houston knows first hand how involvement in research as an undergraduate can have a
significant impact.

“I think a unique part of what we do here at New Mexico State is provide a lot of research opportunity for undergrads,” Houston said. “My undergrads, they run projects. They’re growing cells. They’re treating cells. They’re presenting data. Here we have a true balance between research and teaching. I was an undergraduate researcher here in the 90s and it basically changed my life. A research experience can help students in the sciences with whatever they want to do.”

The goal of Houston’s research is to benefit breast cancer patients. By better understanding tamoxifen or anti-estrogen treatment resistance, he and his team seek to identify resistance in its early stages so doctors can change treatments and provide better patient care. Although it’s an area Houston may not have initially planned to pursue, it has resulted in an opportunity for cancer research at NMSU yielding results both in the classroom and the lab.

“Kevin's new project is a perfect example of how discoveries in science can occur,” Arterburn said. “You may be studying one question but by observing carefully, working diligently and thinking creatively you can find a new key to the lock hidden in your results, or a different direction to look that gives another reason to hope that we will be able to stop cancer."