Reference SummaryEngelman RW, Cancer Res 1993 Mar 1;53(5):1188-94

Title	Calories, parity, and prolactin influence mammary epithelial kinetics and differentiation and alter mouse mammary tumor risk.
Authors	Engelman RW; Day NK; Good RA
Journal	Cancer Res
Volume	53
Issue	5
Year	1993
Pages	1188-94
Abstract	Reduced calorie intake (RCI) suppresses mouse mammary tumor virus (MMTV) transcription and reduces mammary tumor (MT) incidence in C3H/Ou mice. Since efficient retroviral expression requires cell division, we investigated whether the suppression of MMTV and MT by RCI reflects changes in mammary histogenesis and lowered epithelial kinetics. Prolactin (PRL) augments MMTV transcription. Since PRL levels may be lowered by RCI, we evaluated whether lowered PRL in ad libitum-fed mice alters mammary histogenesis and MT incidence in a manner comparable to RCI. Pregnancy augments MMTV transcription. Hence, we also determined the effect of parity on mammary histogenesis, kinetics, and MT risk. One hundred thirty-five C3H/Ou mice were fed ad libitum or a RCI level and separated into six experimental groups. Twenty ad libitum-fed mice were injected with a dopaminomimetic to lower PRL, and 20 RCI mice were engrafted with adenohypophyses to elevate PRL. Twenty-seven ad libitum-fed mice and twenty-eight RCI mice experienced a single parturition. RCI protected nulliparous (P = 0.0001) and parous mice (P = 0.005) from MT development. Reduced calories or lowered PRL with ad libitum feeding similarly influenced mammary histogenesis, kinetics and MT risk (P > 0.5). Mammary glands of RCI mice or of ad libitum-fed mice with lowered PRL were histologically comparable and principally ductular with a low DNA-labeling index (DNA-LI) (P < 0.001). In contrast, the parenchyma of ad libitum-fed mice or of RCI mice with elevated PRL had exuberant alveoli formation, an elevated DNA-LI (P < 0.001), and preneoplastic lesions. Parity did not change the elevated DNA-LI and MT risk of ad libitum-fed mice but increased the mammary DNA-LI (P < 0.001) and MT incidence (P = 0.01) of RCI mice. Prevention of mammary tumorigenesis in C3H/Ou mice by RCI may result from modulated serum PRL activity and reduced mammary epithelial kinetics which suppress MMTV transcription and minimize the risk of activating protooncogenes.
Links	J:4072 – MGI References 8382558 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency	Model Details
C3H/HeOuJ	Mammary gland adenocarcinoma		Mammary gland	100
C3H/HeOuJ	Mammary gland adenocarcinoma	CV205502 (prolactin inhibitor)	Mammary gland	50
C3H/HeOuJ	Mammary gland adenocarcinoma	calorie restricted	Mammary gland	21 - 72
C3H/HeOuJ	Mammary gland adenocarcinoma	calorie restricted pituitary isograft	Mammary gland	100
C3H/HeOuJ	Mammary gland hyperplasia - alveolar		Mammary gland	observed
C3H/HeOuJ	Mammary gland hyperplasia - alveolar	CV205502 (prolactin inhibitor)	Mammary gland	0
C3H/HeOuJ	Mammary gland hyperplasia - alveolar	calorie restricted	Mammary gland	0
C3H/HeOuJ	Mammary gland hyperplasia - alveolar	calorie restricted pituitary isograft	Mammary gland	observed