Fuchs-Young, Robin

Fuchs-Young, Robin Ph.D.

Selected Publications  |  Search PubMed  |  Contact

Research Interests

Breast cancer, hormone action, crosstalk, growth hormones, p53, hormonal carcinogenesis, obesity

Current Research

The main focus of my laboratory is the study of hormonal control of breast cancer, including crosstalk between hormone and growth factors signaling pathways. The goal of our research is to advance our understanding of how steroids and other hormones affect tissue development and tumorigenesis and to identify pivotal molecular targets involved in these processes. The scope of the research includes evaluation of the mechanisms by which hormones interact with IGF-1 and p53 to regulate tumor development and progression. Our investigations utilize both in vitro and in vivo systems but identification and characterization of novel transgenic and knockout animal models of tumorigenesis are especially important.

One of the major projects in the lab focuses on the interrelationship between expression of estrogen receptor (ER) and p53. ER and the p53 tumor suppressor are both prognostic indicators for breast cancer. Assessment of these factors provides insight into likelihood of disease progression, survival and response to hormonal ablation therapies. ER is known to be an indicator of good prognosis, predicting beneficial response to antiestrogens and increased overall survival. Loss of p53 is associated with a worse prognosis and increased likelihood of tumor progression.

Our lab has conducted in vivo experiments showing that ER expression is also dependent on p53 status in mammary tumors. In vitro analyses have demonstrated that stimulation of p53 expression with ionizing radiation or chemotherapeutics also increases ER expression. Conversely, knockdown of p53 is associated with reductions in ER. Our data suggest that expression of these two important tumor markers is linked, possibly as part of a regulatory loop controlling the balance between proliferation and apoptosis.

A second major project focuses on the role of IGF-1 in mammary tumorigenesis. To clarify the role of IGF-I in mammary tumorigenesis in vivo, we are using a unique transgenic model, in which over-expression of IGF-I is under the control of the bovine keratin 5 (BK5) promoter. In the BK5.IGF-1 model, IGF-I transgene expression in the mammary gland occurs exclusively in the myoepithelial cells, thus mimicking the paracrine effects of stromal IGF-I on mammary epithelial cells.

Our studies also demonstrate that paracrine IGF-I stimulates mammary tumorigenesis, even in the absence of exogenous carcinogen. Interestingly, mammary adenocarcinomas arising in the BK5.IGF-1 transgenics are ER and PR positive. Signaling analyses show that the stimulatory effects of IGF-1 in the mammary gland are primarily being mediated through the PI3K-Akt pathway. Recent in vivo studies indicate that in the absence of ER, the stimulatory actions of IGF-1 on the mammary gland are lost. These results indicate that ER is a required mediator of the effects of IGF-1 in the mammary gland.

Recently, the lab has begun collaborative investigations on the role of IGF-1 in mediating the effects of obesity and metabolic syndrome on mammary carcinogenesis. Using the BK5.IGF-1 model, we have demonstrated that calorie restriction (CR) is effective in reducing tumorigenesis, even though IGF-1 levels are not affected.

We anticipate that our studies will provide a better understanding of how endogenous processes can modulate tumor development and progression in hormonally responsive tissues. We hope that these investigations will provide improved strategies for prevention and treatment of breast cancer.

Selected Publications

  1. Benavides F, Gomez G, Venables-Griffith A, Lambertz I, Flores M, Angel JM, Fuchs-Young R, Richie ER, Conti CJ. Differential susceptibility to chemically induced thymic lymphomas in SENCARB and SSIN inbred mice, Mol Carcinog, 45 (7), 543-8, 2006
  2. Yakar S, Nunez NP, Pennisi P, Brodt P, Sun H, Fallavollita L, Zhao H, Scavo L, Novosyadlyy R, Kurshan N, Stannard B, East-Palmer J, Smith NC, Perkins SN, Fuchs-Young R, Barrett JC, Hursting SD, Leroith D. Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones, Endocrinology, 147 (12), 5826-34, 2006
  3. Burroughs KD, Howe SR, Okubo Y, Fuchs-Young R, LeRoith D, Walker CL. Dysregulation of IGF-I signaling in uterine leiomyoma, J Endocrinol, 172 (1), 83-93, 2002
  4. Fuchs-Young R, Preclinical studies of raloxifene and related compounds, in Hormone Therapy in Breast and Prostate Cancer, edited by Jordan VC, Furr B, pp. 133-59, Humana Press, Inc., Totowa, NJ, 2002
  5. Burroughs KD, Fuchs-Young R, Davis BJ, Walker CL. Altered hormonal responsiveness of proliferation and apoptosis during myometrial maturation and the development of uterine leiomyomas in the rat, Biol Reprod, 63 (5), 1322-30, 2000
  6. Gamage SD, Bischoff ED, Burroughs KD, Lamph WW, Gottardis MM, Walker CL, Fuchs-Young R. Efficacy of LGD1069 (Targretin), a retinoid X receptor-selective ligand, for treatment of uterine leiomyoma, J Pharmacol Exp Ther, 295 (2), 677-81, 2000
  7. Walker CL, Burroughs KD, Davis BJ, Sowell K, Everitt JI, Fuchs-Young R. Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma, J Soc Gynecol Investig, 7 (4), 249-56, 2000

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9513