1: Endocr Relat Cancer. 2005 Jun;12(2):319-34. 

RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation
of genes involved in regulation of the immune response.

Puxeddu E, Knauf JA, Sartor MA, Mitsutake N, Smith EP, Medvedovic M, Tomlinson
CR, Moretti S, Fagin JA.

Division of Endocrinology and Metabolism, University of Cincinnati College of
Medicine, Cincinnati, Ohio 45267, USA.

RET/PTC rearrangements represent key genetic events involved in papillary
thyroid carcinoma (PTC) initiation. The aim of the present study was to identify
the early changes in gene expression induced by RET/PTC in thyroid cells. For
this purpose, microarray analysis was conducted on PCCL3 cells conditionally
expressing the RET/PTC3 oncogene. Gene expression profiling 48 h after
activation of RET/PTC3 identified a statistically significant modification of
expression of 270 genes. Quantitative PCR confirmation of 20 of these
demonstrated 90% accuracy of the microarray. Functional clustering of genes with
greater than or less than 1.75-fold expression change (86 genes) revealed
RET/PTC3-induced regulation of genes with key functions in apoptosis (Ripk3,
Tdga), cell-cell signaling (Cdh6, Fn1), cell cycle (Il24), immune and
inflammation response (Cxcl10, Scya2, Il6, Gbp2, Oas1, Tap1, RT1Aw2, C2ta, Irf1,
Lmp2, Psme2, Prkr), metabolism (Aldob, Ptges, Nd2, Gss, Gstt1), signal
transduction (Socs3, Nf1, Jak2, Cpg21, Dusp6, Socs1, Stat1, Stat3, Cish) and
transcription (Nr4a1, Junb, Hfh1, Runx1, Foxe1). Genes coding for proteins
involved in the immune response and in intracellular signal transduction
pathways activated by cytokines and chemokines were strongly represented,
indicating a critical role of RET/PTC3 in the early modulation of the immune
response.

PMID: 15947106 [PubMed - indexed for MEDLINE]


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2: Exp Cell Res. 2005 Feb 1;303(1):79-88. 

GDNF-induced leukemia inhibitory factor can mediate differentiation via the
MEK/ERK pathway in pheochromocytoma cells derived from nf1-heterozygous knockout
mice.

Park JI, Powers JF, Tischler AS, Strock CJ, Ball DW, Nelkin BD.

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School
of Medicine, Baltimore, MD 21231, USA. jpark15@jhmi.edu

Glial cell line-derived neurotrophic factor (GDNF) can induce neuron-like
differentiation of mouse pheochromocytoma (MPC) cell lines derived from mice
with a heterozygous knockout mutation of nf1, the murine counterpart of the
human gene mutated in neurofibromatosis type 1 (NF1). Here, we show that
GDNF-induced differentiation in the MPC 862L cell line is mediated by the
MEK/extracellular signal-regulated kinase (ERK) pathway. Neurite outgrowth,
increased expression of growth-associated protein 43, and decreased
incorporation of bromodeoxyuridine (BrdU) were induced by treatment with GDNF,
H-RasV12, or a constitutively active MEK2. GDNF also induces leukemia inhibitory
factor (LIF) via the MEK/ERK pathway, and LIF itself can elicit these
differentiative changes via a cell-extrinsic autocrine/paracrine pathway.
Treatment with anti-LIF neutralizing antibody depleted the differentiative
activity of the conditioned medium from cells stimulated for MEK/ERK signaling,
while recombinant LIF could induce differentiation in MPC cells, indicating that
LIF is the sole factor with differentiative activity. LIF could activate MEK1/2
and STAT3, but LIF-induced differentiation was blocked only by the
MEK1/2-specific inhibitor U0126, indicating that the MEK/ERK pathway is
necessary for LIF action in MPC cells. Our findings suggest that LIF may be
utilized for signaling mediated by GDNF and may be important in the pathobiology
of neuroendocrine tumors.

PMID: 15572029 [PubMed - indexed for MEDLINE]


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3: J Mammary Gland Biol Neoplasia. 1999 Apr;4(2):145-52. 

Transcription factor activities and gene expression during mouse mammary gland
involution.

Marti A, Lazar H, Ritter P, Jaggi R.

Department for Clinical Research, University of Bern, Switzerland.

Maintenance of mammary epithelial differentiation and milk production during
lactation is a consequence of milk removal and the presence of lactogenic
hormones, particularly glucocorticoids, insulin and prolactin. After weaning the
fall in lactogenic hormones and milk stasis lead to involution, a process that
is mainly characterized by three events: (i) downregulation of milk protein gene
expression, (ii) loss of epithelial cells by apoptosis and, (iii) tissue
remodeling and preparation of the gland for a new pregnancy. Each of these
processes is likely to depend on the activity of specific sets of transcription
factors in the mammary epithelium and stroma that ensure the timely and
spatially coordinated expression of critical gene products such as mediators of
apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g.,
matrix metalloproteinases). Here we describe signal transduction events such as
activation of protein kinase A and JNK and changes in the activity of several
transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the
early and late phases of mammary gland involution. We discuss their possible
role in regulating and coordinating involution with emphasis on the apoptotic
process of involution.

Publication Types:
    Review
    Review, Tutorial

PMID: 10426393 [PubMed - indexed for MEDLINE]


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