Cell proliferation is regulated by the induction of growth promoting genes and the suppression of growth inhibitory
genes. Malignant growth can result from the altered balance of expression of these genes in favor of cell proliferation.
Induction of the transcription factor MYC promotes cell proliferation and transformation by activating
growth-promoting genes.
General function
Cell death/survival, Oncogenesis, Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Follicle development
Comment
Expression regulated by
FSH, LH, Steroids
Comment
Delidow BC, et al 1990 reported the gonadotropin induction of c-fos and c-myc expression and
deoxyribonucleic acid synthesis in rat granulosa cells.
In this study the acute effects of PMSG on protooncogene expression,
DNA synthesis, and steroid secretion were examined. The levels of c-fos, c-myc,
and beta-actin mRNA were measured in total RNA samples from granulosa cells
by quantitative polymerase chain reaction. PMSG increased the mRNA levels of
c-fos, c-myc, and beta-actin within 15 min. Fos and myc proteins were localized
within granulosa cells by immunocytochemistry. Less than 10% of granulosa cells
stained for c-fos or c-myc proteins in the control samples. In contrast,
approximately 40% of the cells stained for these protooncogene proteins 30 min
after PMSG injection (P less than 0.05). These values declined to about 10% of
the cells 60 min after PMSG injection.
Delidow BC et al 1992 reported regulation of proto-oncogene expression and deoxyribonucleic
acid synthesis in granulosa cells of perifused immature rat
ovaries.
In the first study, granulosa cells (GCs) were harvested from
immature rat ovaries after 15, 30, or 60 min of perifusion and DNA synthesis
(3H-thymidine incorporation) and proto-oncogene mRNA levels were
determined. The presence of c-myc and c-fos proteins was localized within GCs
immunocytochemically. GCs of control ovaries exhibited modest levels of DNA
synthesis and proto-oncogene expression. FSH/insulin (IN) not only stimulated DNA
synthesis but also increased c-myc, c-fos, and c-jun mRNA levels and the
percentage of cells staining for c-fos and c-myc proteins.
Ovarian localization
Oocyte, Granulosa, Luteal cells
Comment
Expression of c-MYC in Nuclear Speckles During Mouse Oocyte Growth and Preimplantation Development. Suzuki T et al. Myelocytomatosis oncogene (c-myc) is a major transcriptional regulator that controls various biological processes, and its deregulated expression causes carcinogenesis. To investigate the involvement of c-myc in oogenesis and preimplantation development, the expression of c-MYC during these stages was examined by immunocytochemistry. A strong c-MYC signal was detected in the nucleus of growing and fully grown oocytes as well as in preimplantation embryos before the morula stage. The signal intensity decreased slightly at the morula stage, and no signal was detected in blastocysts. Close observation of the nucleus revealed that c-MYC was localized in small granules that appeared to be nuclear speckles controlling pre-mRNA splicing. Although the number of granules decreased during oocyte growth, their size increased. After fertilization, the granules of c-MYC disappeared from the pronuclei, and c-MYC was evenly distributed in the nucleoplasm at the 1-cell stage, but the granules reappeared at the 2-cell stage. These results suggest that c-myc is involved in oocyte growth and preimplantation development and that its role changes during these stages.
Piontkewitz Y, et al reported the expression of c-myc during follicular growth and luteal
formation in the rat ovary in vivo.
C-myc increased rapidly after the administration of both PMSG and hCG, but the effect of PMSG was less pronounced. The increase after PMSG was transient and localized primarily to the
granulosa cells of developing follicles. The ovulatory dose of hCG resulted in a
rapid and substantial increase of c-myc mRNA and protein with maximal levels at
1 h and 2-4 respectively. At this stage, the c-myc protein was localized to the
follicular cells, the surface epithelium and, to some extent, to the interstitial tissue.
There was a subsequent decrease prior to ovulation. The luteal phase was
characterized by decreasing levels of c-myc with increasing luteal age. Hypophysectomy resulted in a decrease
of c-myc compared with intact animals. The administration of E2 resulted in an
increase of c-myc mRNA and protein. The subsequent treatment with FSH did not
result in a further increase and the levels remained at the same level as with E2
only. However, an ovulatory dose of hCG to E2 and FSH primed animals resulted
in an additional increase of c-myc mRNA and protein.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - non-ovarian defect Comment:Davis AC, et al 1993 reported that a A null c-myc mutation causes lethality before 10.5 days of
gestation in homozygotes and reduced fertility in heterozygous
female mice.
The
analysis of embryos from two clones has shown that the mutation is lethal in
homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally
smaller and retarded in development compared with their littermates. Pathologic
abnormalities include the heart, pericardium, neural tube, and delay or failure in
turning of the embryo. Heterozygous females have reduced fertility owing to
embryonic resorption before 9.5 days of gestation in 14% of implanted embryos.
c-Myc protein is necessary for embryonic survival beyond 10.5 days of gestation;
however, it appears to be dispensable for cell division both in ES cell lines and
in the embryo before that time.