Gender dimorphism of tumor growth: role of gonadal hormones in differential regulation of apoptosis of a murine T cell lymphoma

Abstract

The present investigation was undertaken to study if a gender-dependent differential induction of tumor cell apoptosis is responsible for the manifestation of gender dimorphism observed in the growth of a transplantable murine T cell lymphoma, designated as Dalton's lymphoma (DL). Tumor cell samples obtained from male tumor-bearing mice showed a higher number of cells with apoptotic morphology compared to that observed in female tumor-bearing mice. In this report we demonstrate that male hormone androgen and female hormone estrogen can differentially modulate tumor cell proliferation and apoptosis through alteration in the expression pattern of cell death regulating genes: p53 and CAD. DL cells were shown to express mRNA for androgen and estrogen receptors. Further these gonadal hormones also induced tumor cells to produce tumor growth regulating proteins: VEGF, TGF-beta, IL-2, IL-2R, SOCS, Hsp-70 and IFN-gamma which in turn either through autocrine action on tumor cells or via TAM-derived NO were observed to regulate tumor cell apoptosis leading to gender dimorphism of tumor growth. This study also discusses the possible mechanism involved. The study has clinical significance as these results will helps in understanding the mechanism of gender dimorphism with respect to the progression of T-cells tumors.