| First Author | Engelman RW | Year | 1993 |
| Journal | Cancer Res | Volume | 53 |
| Issue | 5 | Pages | 1188-94 |
| PubMed ID | 8382558 | Mgi Jnum | J:4072 |
| Mgi Id | MGI:52573 | Citation | Engelman RW, et al. (1993) Calories, parity, and prolactin influence mammary epithelial kinetics and differentiation and alter mouse mammary tumor risk. Cancer Res 53(5):1188-94 |
| abstractText | 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. |
