Reference SummaryTennent BJ, Cancer Res 1993 Mar 1;53(5):1059-63

Title

Genetic susceptibility for C19 androgen induction of ovarian granulosa cell tumorigenesis in SWXJ strains of mice.

Authors

Tennent BJ; Shultz KL; Beamer WG

Journal

Cancer Res

Volume

53

Issue

5

Year

1993

Pages

1059-63

Abstract

Susceptibility to pubertal onset, malignant granulosa cell (GC) tumors of the ovary is inherited in SWR/Bm and certain SWR-related SWXJ recombinant inbred strains of mice. In some SWXJ strains, GC tumors occur spontaneously (spontaneous strains), and in others GC tumors can only be induced by treatment with dehydroepiandrosterone (DHEA-dependent strains). A gene controlling susceptibility to both spontaneous and DHEA-induced GC tumorigenesis, Gct, has been assigned to Chromosome 4. Additional research on the role of steroids in GC tumorigenesis has revealed a second gene controlling response to C19 androgenic steroids. Spontaneous strains showed increased tumor frequency after treatment with testosterone (T), whereas DHEA-dependent strains showed no GC tumors following T treatment. Within treatment groups, serum steroid data from DHEA, T, and control treated mice showed no consistent differences between spontaneous and DHEA-dependent strains with respect to progesterone, DHEA, androstenedione, dihydrotestosterone, T, estrone, or estradiol. Thus, observed differences in GC tumor responsiveness to exogenous steroids were not due to different patterns of steroid metabolism among spontaneous and DHEA-dependent strains. Further studies on the range of effective C19 steroids were conducted using one spontaneous and one DHEA-dependent strain. The spontaneous strain showed increased GC tumor frequency in response to dihydrotestosterone and androsterone treatment, whereas the DHEA-dependent strain showed no response. This result suggests that spontaneous strains may be sensitive to a broad range of C19 steroids. To determine whether genetic differences in endogenous steroid levels have a role in spontaneous GC tumorigenesis, serum steroid levels were measured in SWR/Bm and SJL/Bm progenitor strains during the developmental period of risk between 22 and 38 days of age. With the exception of transiently increased DHEA at 22 days, there were no consistent differences in steroid levels analyzed. Thus, serum steroid profiles were not reliably prognostic for GC tumorigenesis. In conclusion, GC tumor induction in response to T treatment has co-segregated with susceptibility to spontaneous GC tumors in the SWXJ recombinant inbred strains. Thus, the second gene in our ovarian granulosa cell tumor model regulates responsiveness to T. We propose to name this gene spontaneous ovarian tumorigenesis (Sot), with alleles for susceptibility (s) carried by spontaneous strains and resistance (r) carried by DHEA-dependent strains.

Links

J:4202 – MGI References
8439952 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
SWR/Bm Ovary - Granulosa cell tumor Ovary - Granulosa cell

2.5

SWR/Bm Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

24

SWR/Bm Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

17

SWXJ1/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

1.8

SWXJ1/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

18

SWXJ1/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

8.7

SWXJ4/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

1.2

SWXJ4/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

8.2

SWXJ4/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

12

SWXJ8/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

0.4

SWXJ8/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

44

SWXJ8/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

11

SWXJ9/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

41

SWXJ9/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

34

SWXJ6/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

SWXJ6/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

11

SWXJ6/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

0

SWXJ7/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

SWXJ7/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

14

SWXJ7/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

0

SWXJ10/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

SWXJ10/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

2.8

SWXJ10/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

0

SWXJ12/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

SWXJ12/BmJ Ovary - Granulosa cell tumor
  • dehydroepiandrosterone (DHEA)
Ovary - Granulosa cell

8.3

SWXJ12/BmJ Ovary - Granulosa cell tumor
  • testosterone
Ovary - Granulosa cell

0

SWXJ9/BmJ Ovary - Granulosa cell tumor Ovary - Granulosa cell

4.7 - 6.6

SWXJ9/BmJ Ovary - Granulosa cell tumor
  • dihydrotestosterone (DHT)
Ovary - Granulosa cell

23

SWXJ9/BmJ Ovary - Granulosa cell tumor
  • androsterone
Ovary - Granulosa cell

21

SWXJ7/BmJ Ovary - Granulosa cell tumor
  • androsterone
Ovary - Granulosa cell

0

(SWR/Bm x SWXJ9/Bm)F1 Ovary - Granulosa cell tumor Ovary - Granulosa cell

26

(SWR/Bm x SWXJ9/Bm)F1 Ovary - Granulosa cell tumor
  • adrenalectomy
Ovary - Granulosa cell

16 - 28

C57BLKS/J Ovary - Granulosa cell tumor Ovary - Granulosa cell

0