Follicle depletion provides a permissive environment for ovarian carcinogenesis

Yingcai Wang, Kathy Qi Cai, Elizabeth R. Smith, Toni M. Yeasky, Robert Moore, Parvin Ganjei-Azar, Andres J. Klein-Szanto, Andrew K. Godwin, Thomas C. Hamilton, Xiang Xi Xua

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2418-2430
Number of pages13
JournalMolecular and Cellular Biology
Volume36
Issue number18
DOIs
StatePublished - Jan 1 2016

Fingerprint

Metrorrhagia
Carcinogenesis
Ovarian Neoplasms
Adenoma
Neoplasms
Epithelial Cells
Ovarian Follicle
Oviducts
Papilloma
Menopause
Transgenes
Germ Cells
Epidemiologic Studies
Ovary
Mutation
Injections
Incidence
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wang, Y., Cai, K. Q., Smith, E. R., Yeasky, T. M., Moore, R., Ganjei-Azar, P., ... Xua, X. X. (2016). Follicle depletion provides a permissive environment for ovarian carcinogenesis. Molecular and Cellular Biology, 36(18), 2418-2430. https://doi.org/10.1128/MCB.00202-16

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 journalArticle

Wang, Y, Cai, KQ, Smith, ER, Yeasky, TM, Moore, R, Ganjei-Azar, P, Klein-Szanto, AJ, Godwin, AK, Hamilton, TC & Xua, XX 2016, 'Follicle depletion provides a permissive environment for ovarian carcinogenesis', Molecular and Cellular Biology, vol. 36, no. 18, pp. 2418-2430. https://doi.org/10.1128/MCB.00202-16
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. / Follicle depletion provides a permissive environment for ovarian carcinogenesis. In: Molecular and Cellular Biology. 2016 ; Vol. 36, No. 18. pp. 2418-2430.
@article{6ea057b46d1c40ec94dede01cbc586e3,
title = "Follicle depletion provides a permissive environment for ovarian carcinogenesis",
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.",
author = "Yingcai Wang and Cai, {Kathy Qi} and Smith, {Elizabeth R.} and Yeasky, {Toni M.} and Robert Moore and Parvin Ganjei-Azar and Klein-Szanto, {Andres J.} and Godwin, {Andrew K.} and Hamilton, {Thomas C.} and Xua, {Xiang Xi}",
year = "2016",
month = "1",
day = "1",
doi = "10.1128/MCB.00202-16",
language = "English (US)",
volume = "36",
pages = "2418--2430",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "18",

}

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 -