 |
Noreen
Luetteke, Ph.D. Member-in-Residence of the Moffitt Cancer Center E-mail:
Noreen.Luetteke@moffitt.org |
Training
B.A., Northwestern University, Biochemistry 1980
Ph.D., Duke University, Pathology/Cellular and Molecular Biology 1988
Research
Interests
Dr. Luetteke has broad interest and expertise in the regulation of epithelial
function and transformation by polypeptide growth factors and their tyrosine
kinase receptors. Her research program focuses on the erbB family of receptors
and their multiple EGF-related ligands, using both genetic mouse models
and biologically relevant cell culture systems. This family is important
in cancer research because deregulation and/or mutation of erbB receptors,
particulary erbB1 (EGFR) and erbB2 (Neu); or ligands, such as transforming
growth factor alpha (TGFI), amphiregulin (AR), and neuregulins (NRGs);
are clinically and experimentally associated with tumor development and
progression. Dr. Luetteke's earlier work utilized transgenic mice to demonstrate
that overexpression of TGFI was mitogenic and oncogenic in epithelia,
particularly in the gastrointestinal tract and breast. More recently,
gene targeting has revealed distinct physiological roles for TGFI and
AR in hair follicle and mammary ductal morphogenesis, respectively. The
nature of the defects in ligand knockout mice suggest that these growth
factors contribute in a tissue-specific manner to epithelial-mesenchymal
interactions and control of cell migration as well as cell proliferation.
Dr. Luetteke's laboratory is further investigating potential downstream
signaling pathways of these growth factors in the contexts of skin and
mammary gland. Her current funded project studies the expression, interactions
and functions of erbB receptors in skin during development and repair.
One approach is the derivation of transgenic mice expressing an epitope-tagged,
dominant-negative form of erbB2 in the basal epidermis. Though still considered
an orphan receptor, erbB2 preferentially heterodimerizes with and activates
the other erbB members in response to their ligands. Thus, a dominant-negative
erbB2 could potentially disrupt signaling from multiple erbB receptors
and ligands. Dr. Luetteke plans to examine the effects of this mutant
on wound healing and skin carcinogenesis in vivo; and receptor interactions,
signal transduction and cell behavior in vitro in primary cultures of
keratinocytes. Another project under development is the derivation of
transgenic mouse models of EGFR and erbB2 function in bladder cancer.
Overexpression of these receptors in human bladder cancer correlates with
disease recurrence and progression and poor prognosis, but their causal
role is controversial. Since EGF and related ligands are excreted in urine
and secreted by bladder tumor cells, persistent receptor activation could
lead to abnormal growth or invasion. These receptor transgenic and ligand
knockout mouse strains will provide model systems to investigate the chronologic
and mechanistic contribution of this signaling system to tumorigenesis.
Search
for publications by: 
This
search will be conducted at the US National Library of Medicine (NLM) and PubMed.
Selected
Publications
Luetteke NC, Qiu TH, Fenton SE, Troyer KL, Riedel RF, Chang A, Lee DC
(1999) Targeted inactivation of the EGF and amphiregulin genes reveals
distinct roles for EGF receptor ligands in mouse mammary gland development.
Development 126:2739-50.
Luetteke NC, Phillips HK, Qiu TH, Copeland NG, Earp HS, Jenkins NA, Lee DC (1994) The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev 8:399-413.
Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC (1993) TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 1993 73:263-78. Sandgren, EP,
Luetteke, NC, Qiu, TH, Palmiter, RD, Brinster, RL, and Lee, DC (1993). Transforming growth factor alpha dramatically enhances oncogene-induced carcinogenesis in transgenic mouse pancreas and liver. Mol. Cell. Biol. 13:320-330.
Cancer Biology Ph.D. Program
H. Lee Moffitt Cancer Center, MRC-4 East
12902 Magnolia Drive
Tampa, Florida 33612
Phone: 813-745-6876
E-mail: CancerPHD@moffitt.org
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