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An experimental system for finding out about the cell and genetic biological requirements for breast cancer development has been established. Tumors from transformed primary human mammary epithelial cells (HMECs), transformed by introducing specific genes are badly differentiated carcinomas that grow into nearby tissue. Introducing three genes into primary HMECs gives cells that form tumors when transplanted into the mammary glands of immunocompromised mice or transplanted subcutaneously. The three are genes that encode the telomerase-catalytic subunit, the SV40 large-T antigen, and an H-Ras oncoprotein. The combinations of mutations necessary together to form breast cancer cells are not known.

The failure of the ovarian granulosa cells to proliferate in response to the follicle-stimulating hormone (FSH) leads to sterility in cyclin D2-deficient female mice and hypoplastic testes in D2-deficient male mice. Human ovarian granulosa cell tumors and testicular germ-cell tumors express high levels of cyclin D2 mRNA compared to the normal ovaries and testes. The cyclic-AMP-dependent signaling pathway regulates the expression of the cyclin D2 through FSH.

Mice with deficient cyclin D1 show reduced body size, reduced viability, symptoms of neurological defects and cancerous developments in the retina and the breasts. The retinas of the mice kept under observation demonstrated a striking reduction in cell number due to proliferative failure during embryonic development. In adult mutant females, the breast epithelial cells fail to undergo the massive proliferative changes related with pregnancy despite normals levels of ovarian steroid hormones.

The transcription factor Twist plays an important role in metastasis. The molecular actions of Twist and its involvement in human breast cancer pathogenesis are characterized.