How IGF1 Can Cause Breast Cancer By BCRA1 Gene Negative Regulation By Estrogen?

How IGF1 Can Cause Breast Cancer By BCRA1 Gene Negative Regulation By Estrogen?




The Insulin Like Growth Factor 1 (IGF-1) system
which includes IGF-1, IGF-binding proteins
(IGFBPs) and the IGF-1 receptor (IGF-1R), plays a
significant role in human physiology, particularly in
the development and function of tissues,including
the mammary gland.
IGF-1 R is regulated by SP1(specific protein 1)
transcriptional factors which is stimulated by
estrogen And FGF1 increase by GH
FGF-1 R increase to cell division and
differentiation increase due to downregulation of
cascade of phosphorylation lead to activates the
protein mapk(mitogen activated protein
kinase)and AKT which lead to cell differentiation
and proliferation uncontrolled if not
regulated.These events cause cancer.
BCRA1, P53, WT1 genes normally regulate to
production of IGF1R normal for normal cell
growth, division,proliferation,differentiation.
If BCRA1, P53, WT1 genes mutation and
epigenetics mutations or mismatch repair
unability during breast epithelial cells or stromal
cells division of the mammary gland lead to over
expressions of SP1 and uncontrolled transcription
of DNA not inhibit by BCRA1 gene lead to
translation more IGF1R and transport into plasma
membrane lead to receive more IGF,over
expressions of mapk and AKT will cause rapid cell
division without further mismatch repair checking
stimulate more dna damage to more oncogene
activation will cause cancer in breast more
common.
IGF1 also degradation of lysosome and
proteosome and phagosome to inhibit apaptosis,
so damage cell will not apaptosed,and survival
whatever that situation.lead to uncontrolled.
CONCLUSION:Breast require normal amout of
IGFR1 for normal growth, some female lack IGF1R
can cause abnormal hypomastia,Estrogen is also
the stimuli for FGF1R gene activation,so the high
amount of estrogen also indirect for causing
breast cancer or hypermastia rather than
normomastia
DRUG TREATMENT:FIGHTUMUMAB is IGF1R
inhibitors
IGF1RTKI(IGF1 receptor tyrosine kinase inhibitors)



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