Abstract
We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in postmenopausal women.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2418-2430 |
| Number of pages | 13 |
| Journal | Molecular and Cellular Biology |
| Volume | 36 |
| Issue number | 18 |
| DOIs | |
| State | Published - Jan 1 2016 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Follicle depletion provides a permissive environment for ovarian carcinogenesis. / Wang, Yingcai; Cai, Kathy Qi; Smith, Elizabeth R.; Yeasky, Toni M.; Moore, Robert; Ganjei-Azar, Parvin; Klein-Szanto, Andres J.; Godwin, Andrew K.; Hamilton, Thomas C.; Xua, Xiang Xi.
In: Molecular and Cellular Biology, Vol. 36, No. 18, 01.01.2016, p. 2418-2430.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Follicle depletion provides a permissive environment for ovarian carcinogenesis
AU - Wang, Yingcai
AU - Cai, Kathy Qi
AU - Smith, Elizabeth R.
AU - Yeasky, Toni M.
AU - Moore, Robert
AU - Ganjei-Azar, Parvin
AU - Klein-Szanto, Andres J.
AU - Godwin, Andrew K.
AU - Hamilton, Thomas C.
AU - Xua, Xiang Xi
PY - 2016/1/1
Y1 - 2016/1/1
N2 - We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in postmenopausal women.
AB - We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in postmenopausal women.
UR - http://www.scopus.com/inward/record.url?scp=84988354161&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988354161&partnerID=8YFLogxK
U2 - 10.1128/MCB.00202-16
DO - 10.1128/MCB.00202-16
M3 - Article
C2 - 27354067
AN - SCOPUS:84988354161
VL - 36
SP - 2418
EP - 2430
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 18
ER -