Progesterone limits the tumor-promoting effects of the beta-subunit of human chorionic gonadotropin via non-nuclear receptors

Moumita Sarkar; Harsh Sharma; Parminder Singh; Ranbala Ranu; Ravi Datta Sharma; Usha Agrawal; Rahul Pal

doi:10.1016/j.isci.2022.104527

Progesterone limits the tumor-promoting effects of the beta-subunit of human chorionic gonadotropin via non-nuclear receptors

iScience. 2022 Jun 3;25(7):104527. doi: 10.1016/j.isci.2022.104527. eCollection 2022 Jul 15.

Authors

Moumita Sarkar¹, Harsh Sharma², Parminder Singh³, Ranbala Ranu⁴, Ravi Datta Sharma², Usha Agrawal⁴, Rahul Pal¹

Affiliations

¹ Immunoendocrinology Lab, National Institute of Immunology, New Delhi, Delhi 110067, India.
² Amity Institute of Integrative Sciences and Health, Amity University, Gurugram, Haryana 122413, India.
³ Larry L. Hillblom Center, Buck Institute for Research on Aging, Novato, CA 94945, USA.
⁴ Cancer Research Imaging and Biobanking Lab, National Institute of Pathology, New Delhi, Delhi 110029, India.

Abstract

The post-menopausal state in women is associated with increased cancer incidence, the reasons for which remain obscure. Curiously, increased circulating levels of beta-hCG (human chorionic gonadotropin) (a hormonal subunit linked with tumors of several lineages) are also often observed post-menopause. This study describes a previously unidentified interplay between beta-hCG and progesterone in tumorigenesis. Progesterone mediated apoptosis in beta-hCG responsive tumor cells via non-nuclear receptors. The transgenic expression of beta-hCG, particularly in the absence of the ovaries (a mimic of the post-menopausal state) constituted a potent pro-tumorigenic signal. Significantly, the administration of progesterone had significant anti-tumor effects. RNA-seq profiling identified molecular signatures associated with these processes. TCGA analysis revealed correlates between the expression of several newly identified genes and poor prognosis in post-menopausal patients of lung adenocarcinoma, colon adenocarcinoma, and glioblastoma. Specifically in these women, the detection of intra-tumoral/extra-tumoral beta-hCG may serve as a useful prognostic indicator, and treatment with progesterone on its detection may prove beneficial.

Keywords: Cancer; Cell biology; Physiology.