Unit:
Τομέας Βασικών ΕπιστημώνLibrary of the School of Health Sciences
Author:
Mourmouras Nikolaos
Dissertation committee:
1. Μιχαήλ Κουτσιλιέρης, Καθηγητής, Ιατρική, ΕΚΠΑ
2. Κων/ος Κωνσταντινίδης, Καθηγητής, Ιατρική, ΕΚΠΑ
3. Μαρία Λυμπέρη , Αναπληρώτρια Καθηγήτρια,Ιατρική, ΕΚΠΑ
4. Ελένη Κοτσιφάκη, Αναπληρώτρια Καθηγήτρια,Ιατρική, ΕΚΠΑ
5. Παναγούλα Αγγελογιάννη, Αναπληρώτρια Καθηγήτρια,Ιατρική, ΕΚΠΑ
6. Αθανάσιος Αρμακόλας, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
7. Αναστάσιος Φιλίππου, Επίκουρος Καθηγητής,Ιατρική, ΕΚΠΑ
Original Title:
Η έκφραση των ισομορφών του IGF-I στον καρκίνο της ουροδόχου κύστης
Translated title:
The expression of isoforms of IGF-I in the bladder cancer
Summary:
Bladder cancer is the second most common cancer of the urinary tract after prostate cancer.
Bladder cancer accounts for about 2,6% of deaths from cancer in men and 1,4% in women.
IGFs are composing a complex regulatory system witch consists of two binding factors ( IGF-I, IGFII),
One receptor(IGF-IR) and six binding proteins (IGFBPs). IGF-I is produced primarly by the liver as an
endocrine hormone. Production is stimulated by Growth Hormone (GH.) Approximately 99% of IGF-1
is always bound to one of 6 binding proteins (IGF-BP). Only as small percentage ( <5%) constitute its
biologically active fraction. IGF-I binding to its receptor IGF1-R initiates intracellular signaling.
IGF1 gene is located in chromosome 12 (Cytogenetic Location: 12q23.2, which is the long (q) arm of
chromosome 12 at position 23.2) Alternative splicing results in multiple transcript variants encoding
different isoforms that may undergo similar processing to generate mature protein.
IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth
and proliferation, and a potent inhibitor of programmed cell death . This combination strongly suggests the role
of this factor in the procedure of tumorigenesis. The IGF signaling pathway is implicated in many cancer types
such as sarcoma, leukemia , prostate cancer, breast cancer, lung cancer, colon cancer, gastric cancer, cancer of
esophagus, liver cancer, pancreatic cancer, kidney cancer, thyroid gland cancer, brain cancer, ovarian cancer and
uterine cancer.
At this time no specific tumor markers have been found to play major role in the diagnosis and follow up of
patients with bladder cancer. A positive correlation between high serum level of IGF 1 and high risk of developing
several cancer types has been reported. IGF 1 and its specific receptor IGF-R seem to play a role in the development
of bladder cancer especially through uncontrolled and ubnormal cell growth and proliferation. Patients diagnosed with
bladder cancer show high serum level of IGF 1 compared to general population. There is also a positive correlation
between the expression of IGF 1 and the recurrency rate of bladder cancer. Probably in future IGF 1 could be used
as screening test for general population as for example PSA is used now for prostate cancer.
As already said IGF 1 plays a major role in tumorigenesis. However there are few studies as far as IGF isoforms are
Concerned and they are basically referring to prostate cancer, colon cancer, uterine cancer and multiple myeloma.
At this moment there is no available literature about the role of isoforms of IGF-I to bladder cancer.
This thesis means to study the expression of isoforms of IGF-I in malignant urothelium compared to normal urothelium
At an mRNA basis. Finding new cellular and molecular mechanisms that participate in tumorigenesis could have a wide apply
On everyday practice, both in diagnosis with the finding of a specific molecular marker and in treatment with the development of
New “targeted treatment”
In the current study forty six people, both men and women diagnosed with urothelium cancer participated. During operation
Pathological and normal tissue were taken for examination, in every single patient. In laboratory tissues were processed with real
Time PCR and were checked for the expression of isoforms of IGF-I at transcription level.(mRNA)
All samples were found to show a non statistically significant increased expression of isoforms IGF-IEa and IGF-IEb in pathological
Urothelial tissues compared to normal ones. In addition statistically significant decreased expression of IGF-IEc was noted in malignant
Urothelial tissues. Same model of expressions was noted in principal parameters of the disease such as tumors T1 stage, high grade malignancy
Tumors and tumors with macroscopically papillary presentation. These findings are opposite to the current literature according to witch
In the majority of cancers mature IGF-I and isoforms are overexpressed. This result is quite interesting as it seems to agree with the different
Plysiological cellular activities of isoforms that have been proposed and could probably reflect the different role of each isoform in tumorigenesis. Furthermore for the first time is detected the different model of expression in a transcription level (mRNA) of isoform IGF-IEc compared to the other isoforms of IGF-I. This strongly proposes an independent action of MGF both in normal and in cancer cells.
The basic advantage of this thesis is that for the first time we try to recognize the role of isoforms of IGF-I in bladder cancer. This fact could probably erase new questions about the biological action of isoforms and IGF –I both in normal and in cancer cells.
Findings of this Thesis added new data as far as bladder cancer is concerned and in parallel erased new questions witch demand further research.
Main subject category:
Health Sciences
Keywords:
IGF-I, Isoforms IGF-I, bladder cancer
Number of references:
250
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