Kristopher A Lofgren

Kristopher A Lofgren
Gundersen Health System · Medical Research

PhD

About

33
Publications
1,959
Reads
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417
Citations
Additional affiliations
December 2013 - October 2015
Albert Einstein College of Medicine
Position
  • PostDoc Position

Publications

Publications (33)
Article
Full-text available
Basal-type triple-negative breast cancers (TNBC) are aggressive and difficult to treat compared to luminal-type breast cancers. TNBC often express abundant Met receptors and are enriched for transcriptional targets regulated by hypoxia inducible factor 1-alpha (HIF-1α), which independently predicts cancer relapse and increased metastatic risk. Brk/...
Article
Increased vascular permeability contributes to many diseases, including acute respiratory distress syndrome, cancer and inflammation. Most past work on vascular barrier function has focused on soluble regulators, such as tumour-necrosis factor-α. Here we show that lung vascular permeability is controlled mechanically by changes in extracellular mat...
Article
Full-text available
Protein tyrosine kinases (PTKs) are frequently overexpressed and/or activated in human malignancies, and regulate cancer cell proliferation, cellular survival, and migration. As such, they have become promising molecular targets for new therapies. The non-receptor PTK termed breast tumor kinase (Brk/PTK6) is overexpressed in approximately 86% of hu...
Article
Amphiregulin is a transmembrane protein which, when cleaved by the TACE/ADAM17 protease, releases a soluble Epidermal Growth Factor Receptor ligand domain that promotes proliferation of normal and malignant cells. We previously described a rabbit monoclonal antibody, GMF-1A3, that selectively recognizes the cell-associated cleaved Amphiregulin epit...
Article
The EGFR ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is subsequently inter...
Preprint
Amphiregulin (AREG) is a transmembrane protein which, following TACE/ADAM17-dependent cleavage, releases a soluble Epidermal Growth Factor Receptor ligand domain that promotes proliferation of normal and malignant cells. Expression of Amphiregulin has been described by immunohistochemistry in several tumor types, including lung, prostate, head and...
Article
Full-text available
Background The Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transme...
Preprint
Full-text available
The Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stal...
Article
Full-text available
Purpose: The epidermal growth factor receptor ligand, Amphiregulin, is a transcriptional target of estrogen receptor alpha and is required for pubertal mammary gland development. Previous studies using immortalized human breast cancer cell line xenografts have suggested that Amphiregulin may be an important effector of estrogen receptor alpha duri...
Article
Background Targeting of somatic MET mutations using crizotinib has led to strong clinical responses, most frequently in patients with lung cancer, raising the possibility of adopting similar treatment strategies in patients with MET alterations in other cancer types. Patient and Methods We describe a patient with advanced triple-negative breast ca...
Conference Paper
p>Crizotinib is FDA approved in lung cancers with alterations in MET, ROS1 or ALK. Alterations in these genes are also reported in breast cancer, but are very rare and not routinely evaluated. Here we describe two heavily pre-treated patients with metastatic breast cancer treated with off-label single-agent crizotinib following NGS panel detection...
Article
Approximately 266,000 women will be newly diagnosed with invasive breast cancer in the US this year, making it the most prevalent cancer in females, resulting in a 1 in 8 lifetime risk. Many of these tumors are of the hormone receptor positive luminal subtype, with 60-80% expressing the estrogen and/or progesterone receptor (ER+/PR+). The transcrip...
Article
At our center, a standard 25 gene panel has proved useful for the identification of pathogenic germline mutations in many families with a high penetrance of breast and ovarian cancer, yet there remain several families with very high cancer incidence but from whom these assays have not identified pathogenic alleles. To attempt to define the genetic...
Article
Full-text available
Background/aim: GATA3, a transcription factor expressed in luminal breast epithelial cells, is required for mammary gland development. Heterozygous GATA3 mutations occur in up to 15% of estrogen receptor (ER)-positive breast tumors and have been proposed to be null alleles resulting in haploinsufficiency; however, the mutation spectrum of GATA3 in...
Article
Amphiregulin (AREG) is an estrogen-responsive ligand of the epidermal growth factor receptor. Mice with germline deletion of AREG are defective in pubertal mammary expansion. Using shRNA, we have previously reported that the estrogen-responsive growth of MCF7 xenograft tumors in immunocompromised mice is also AREG-dependent. Here we use a series of...
Article
The MET proto-oncogene encodes a receptor tyrosine kinase which is activated by Hepatocyte Growth Factor binding. Recent reports have described single agent activity for crizotinib in MET-amplified or mutant lung adenocarcinoma, squamous cell carcinoma and papillary renal cell carcinoma. Here we describe a stage IV triple-negative breast cancer pat...
Article
Unlike humans, inbred genetically engineered mice have minimal inter-individual variation and, consequently, offer substantially increased statistical power for robust definition of recurrent cooperating cancer mutations. While technically feasible, whole exome sequencing is expensive and extremely data-intensive. Somatic mutation analysis using pa...
Poster
The MET proto-oncogene encodes a receptor tyrosine kinase which is activated by Hepatocyte Growth Factor binding. Recent reports have described single agent activity for crizotinib in MET-amplified or mutant lung adenocarcinoma, squamous cell carcinoma and papillary renal cell carcinoma. Here we describe a stage IV triple-negative breast cancer pat...
Poster
AbstractAmphiregulin (AREG) is an estrogen-responsive ligand of the epidermal growth factor receptor. Mice with germline deletion of AREG are defective in pubertal mammary expansion. Using shRNA, we have previously reported that the estrogen-responsive growth of MCF7 xenograft tumors in immunocompromised mice is also AREG-dependent. Here we use a s...
Article
Triple-negative breast cancer (TNBC) lacks expression of the estrogen and progesterone steroid receptors and HER2; thus TNBC patients cannot benefit from the recent successes of targeted therapies, and instead rely on cytotoxic chemotherapeutic combinations. As such, tumor recurrence is high and patient prognosis is poor. GRB7 is a cytoplasmic adap...
Article
The rate of ultra-late recurrence (beyond 10-15 years) of cutaneous melanoma has been estimated to be between 2.0-6.9% from large case series. Two major factors complicate the interpretation of these data. Firstly, the risk of second primary melanoma is approximately 5% creating uncertainty about whether at least some of these late onset tumors mig...
Article
Ultra-late melanoma recurrence is infrequent, poorly understood and, in most cases, difficult to unambiguously distinguish from a new primary melanoma. We identified a patient with a second melanoma diagnosed after a 30 year disease-free interval, and sought to determine if this new lesion was a recurrence of the original melanoma. Here we report t...
Article
GATA3 is a transcription factor expressed in luminal breast epithelial cells and is required for mammary gland development. Analysis of TCGA data reveals that somatic heterozygous mutations in GATA3 occur in up to 15% of estrogen receptor positive breast tumors, and that these tumors are diagnosed a median of eight years earlier than other estrogen...
Article
Full-text available
Estrogen stimulation promotes epithelial cell proliferation in estrogen receptor (ERα)-positive breast cancer. Many ERα target genes have been enumerated, but the identities of the key effectors mediating the estrogen signal remain obscure. During mouse mammary gland development, the estrogen growth factor receptor (EGFR) ligand amphiregulin acts a...
Article
Triple-negative breast cancer (TNBC) lacks expression of the estrogen and progesterone steroid receptors and HER2; thus TNBC patients cannot benefit from the recent successes of targeted therapies, and instead rely on cytotoxic chemotherapeutic cocktails. As such, tumor recurrence is high and patient prognosis is poor. GRB7 is a soluble adaptor pro...
Article
Full-text available
Signal transduction pathways downstream of receptor tyrosine kinases (RTKs) are often deregulated during oncogenesis, tumor progression, and metastasis. In particular, the peptide growth factor hormone, hepatocyte growth factor (HGF), and its specific receptor, Met tyrosine kinase, regulate cancer cell migration, thereby conferring an aggressive ph...
Article
Full-text available
Total tyrosine kinase activity is often elevated in both cytosolic and membrane fractions of malignant breast tissue and correlates with a decrease in disease-free survival. Breast tumor kinase (Brk; protein tyrosine kinase 6) is a soluble tyrosine kinase that was cloned from a metastatic breast tumor and found to be overexpressed in a majority of...

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