Breast cancer
Colorectal
Carcinomas
Longevity
2007/8-1/29
Ann Surg Oncol. 2007
Jul 26; [Epub ahead of print] Bauer
TW, Fan
F, Liu
W, Camp
ER, Yang
A, Somcio RJ, Bucana CD, Singh
R, Ellis
LM. Department of Surgical
Oncology, The University of Texas M. D. Anderson Cancer Center, 1515
Holcombe Blvd., Houston, TX, 77030, USA. BACKGROUND: Colorectal
carcinomas (CRC) express high levels of insulin-like growth factor-I/II
(IGF-I/II) and the receptor (IGF-IR). We hypothesized that selective inhibition
of IGF-IR would inhibit hepatic growth of human CRC in mice. METHODS: Human
CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody ( PMID: 17653802 [PubMed
- as supplied by publisher] Breast
Cancer Res Treat. 2006 Oct;99(3):323-31. Epub 2006 Jun
5. Fan
J, McKean-Cowdin R, Bernstein
L, Stanczyk FZ, Li
AX, Ballard-Barbash R, McTiernan A, Baumgartner
R, Gilliland
F. Integrated
Substance Abuse Programs, Neuropsychiatric
Institute, Insulin receptor substrate-1
(IRS-1) is a key downstream signaling molecule common to both the insulin
and IGF signaling pathways that can interact with the estrogen pathway to
regulate breast cell growth. We investigated whether a putative functional
variant for IRS-1 (G972R) influences circulating levels of sex hormones,
sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth
factor 1 (IGF-1) levels among post-menopausal African-American and
non-Hispanic white breast cancer patients enrolled in the Health, Eating,
Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones
and growth factors can influence breast cancer recurrence and survival.
Serum estrone, estradiol,
testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at
30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In
African-American patients, the IRS-1 variant was associated with increased
serum levels of estrone (p = 0.02), free estradiol (p = 0.04), total testosterone (p = 0.04), free
testosterone (p = 0.006) and decreased levels of sex hormone-binding
globulin (p = 0.02). No association was present for white patients. Our
findings provide suggestive evidence that IRS-1 G972R variant may be
associated with circulating levels of sex hormones and SHBG in African
American breast cancer survivors. PMID: 16752222 [PubMed
- indexed for MEDLINE] IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB. J
Lab Clin Med. 2006 May;147(5):234-41.
Targeting of Insulin-like
Growth Factor-I Receptor with a Monoclonal Antibody Inhibits Growth of
Hepatic Metastases from Human Colon Carcinoma in Mice.
An association between a
common variant (G972R) in the IRS-1 gene and sex hormone levels in
post-menopausal breast cancer survivors.
Maldonado C,
Cea
P, Adasme
T, Collao
A, Diaz-Araya G,
Chiong
M, Lavandero
S.
Departamento de Bioquimica
y Biologia Molecular, Facultad
de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile;
Centro FONDAP Estudios Moleculares
de la Celula, Universidad de Chile, Santiago,
Chile.
Hyperosmotic stress stimulates a rapid and
pronounced apoptosis in cardiac myocytes which is
attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells
IGF-1 induces intracellular Ca(2+) increase, we
assessed whether the cyclic AMP response element-binding protein (CREB) is
activated by IGF-1 through Ca(2+)-dependent signalling
pathways. In cultured cardiac myocytes, IGF-1
induced phosphorylation (6.5+/-1.0-fold at 5min),
nuclear translocation (30min post-stimulus) and DNA binding activity of
CREB. IGF-1-induced CREB phosphorylation was
mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca(2+)/calmodulin kinase and calcineurin. Exposure of cardiac myocytes
to hyperosmotic stress (sorbitol
600mOsm) decreased IGF-1-induced CREB activation Moreover,
overexpression of a dominant negative CREB
abolished the anti-apoptotic effects of IGF-1. Our results suggest that
IGF-1 activates CREB through a complex signalling
pathway, and this transcription factor plays an important role in the
anti-apoptotic action of IGF-1 in cultured cardiac myocytes.
PMID: 16168389 [PubMed - as supplied by
publisher]
Coordinate activation of intracellular
signaling pathways by insulin-like growth factor-1 and platelet-derived
growth factor in rat hepatic stellate cells.
Bridle
KR, Li
L, O'neill R, Britton
RS, Bacon
BR.
Division of Gastroenterology and Hepatology,
Saint Louis University Liver Center, Saint Louis University School of
Medicine, St. Louis, Missouri.
Proliferation of activated hepatic stellate cells
(HSC) is an important event in the development of hepatic fibrosis.
Insulin-like growth factor-1 (IGF-1) has been shown to be mitogenic for HSC, but the intracellular signaling
pathways involved have not been fully characterized. Thus, the aims of the
current study were to examine the roles of the extracellular
signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3-K) and p70-S6 kinase (p70-S6-K) signaling pathways in IGF-1- and
platelet-derived growth factor (PDGF)-induced mitogenic
signaling of HSC and to examine the potential crosstalk between these
pathways. Both IGF-1 and PDGF increased ERK, PI3-K and p70-S6-K activity.
When evaluating potential crosstalk between these signaling pathways, we
observed that PI3-K is required for p70-S6-K activation by IGF-1 and PDGF,
and is partially responsible for PDGF-induced ERK activation. PDGF and
IGF-1 also increased the levels of cyclin D1 and phospho-glycogen synthase
kinase-3beta. Coordinate activation of ERK, PI3-K and p70-S6-K is important
for perpetuating the activated state of HSC during fibrogenesis.
PMID: 16697771 [PubMed - in process]